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Article in English | WPRIM | ID: wpr-887751


OBJECTIVES@#This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP).@*METHODS@#Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively.@*RESULTS@#The purities of T cells were all >95% in the three groups (@*CONCLUSIONS@#Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.

Chemokine CCL17 , Chemokine CXCL10 , Humans , Lichen Planus, Oral , Ligands , Receptors, CCR4 , Receptors, CXCR3
Article in Chinese | WPRIM | ID: wpr-773559


OBJECTIVE@#To explore the value of interferon-inducible protein 10 (IP-10) in the auxiliary diagnosis of tuberculosis and the judgment of the severity of disease.@*METHODS@#From February, 2013 to February, 2017, a total of 193 patients with TB admitted in our hospital and 84 healthy control subjects were recruited consecutively. The peripheral blood plasma levels of interferon-γ (IFN-γ) and IP-10 were detected using liquid phase chip (Luminex) technique. According to the number of lung fields affected by TB, the patients were divided into group A (with lesions in 1-2 lung fields), group B (3-4 lung fields) and group C (5-6 lung fields), The expressions of IFN-γ and IP-10 in 3 groups were compared.@*RESULTS@#The plasma levels of IP-10 were significantly higher in TB patients than in the control subjects ( < 0.05), but IFN-γ levels were comparable between the two groups ( > 0.05). Among the TB patients, plasma IP-10 levels was the highest in group C ( < 0.05), and IFN-γ levels did not differ significantly among the 3 groups ( > 0.05).@*CONCLUSIONS@#Plasma IP-10 has a certain reference value in the auxiliary diagnosis of active tuberculosis and the judgment of the severity of the disease.

Antigens, Bacterial , Biomarkers , Blood , Chemokine CXCL10 , Blood , Humans , Tuberculosis, Pulmonary , Blood , Diagnosis
Annals of Dermatology ; : 393-402, 2019.
Article in English | WPRIM | ID: wpr-762359


BACKGROUND: Vitiligo is a common acquired pigmentary disease caused by destruction of epidermal melanocytes in underlying autoimmune response. Few studies have been focused on the role of chemokines in non-segmental vitiligo (NSV) concomitant with autoimmune thyroid disease (AITD) and alopecia areata (AA). OBJECTIVE: The aim of this study was to determine the best serum biomarker for predictive role in the progression of vitiligo and to evaluate the influence of AA and/or AITD on vitiligo by using the biomarker. METHODS: This prospective cohort study recruited 45 NSV patients: 14 without either AITD or AA, 12 with AITD, 11 with AA, and 8 with both AITD and AA. Serum levels of CXCL1, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 were analyzed by ELISA. CXCR3 mRNA expression was detected on PBMCs by RT-PCR. Improvement was evaluated using repigmentation scales. RESULTS: Serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with AITD or AA alone than in those without AITD or AA. Moreover, serum CXCL10 levels, along with the expression of CXCR3 mRNA were higher in NSV patients with both AITD and AA than in those with AITD or AA alone. Poorer repigmentation was observed in NSV patients with both AA and AITD than in those with AA or AITD alone. CONCLUSION: CXCL10 could be a biomarker to predict the progression of NSV. Dermatologists should pay much attention to those NSV patients concomitant with AITD and/or AA, for comorbidity might lead to more active autoimmune reaction.

Alopecia Areata , Alopecia , Autoimmunity , Chemokine CXCL10 , Chemokines , Cohort Studies , Comorbidity , Enzyme-Linked Immunosorbent Assay , Humans , Melanocytes , Prospective Studies , RNA, Messenger , Thyroid Diseases , Thyroid Gland , Vitiligo , Weights and Measures
Int. j. odontostomatol. (Print) ; 12(1): 51-56, Mar. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-893303


RESUMEN: El odontólogo como profesional integral del área de la salud, debe tener conocimiento acerca de distintas manifestaciones bioquímicas que pueden tener repercusión en la cavidad oral. El objetivo del trabajo fue determinar las manifestaciones bioquímicas y alteraciones en biomarcadores salivales en la cavidad oral producto de la fibrosis quística o del consumo crónico de medicamentos para el tratamiento de la FQ. Se seleccionó un total de cinco personas con fibrosis quística y cuatro personas sanas, pertenecientes a la ciudad de Concepción en la Octava Región de Chile. Se midió pH salival, capacidad buffer, concentración de proteínas totales, tasa de flujo salival estimulado y se determinó presencia de ciertas enzimas salivales en pacientes que padecen la enfermedad. Se pudo evidenciar que el pH salival en sujetos con fibrosis quística tiende a ser mayor a los valores de referencia, la tasa de flujo salival es mucho menor al igual que la capacidad buffer, la concentración de proteínas totales en saliva se encuentra igual a los valores de referencia y se determinó la presencia biomarcadores salivales a través de la técnica de electroforesis. La fibrosis quística afecta de muchas formas a las personas que la padecen, genera cambios a nivel de los biomarcadores salivales como también en la cavidad oral, por lo que el odontólogo debe estar capacitado para identificar estos cambios y poder tratar de la mejor manera a todo tipo de paciente.

ABSTRACT: The dentist as an integral health professional must have knowledge of various biochemical manifestations that may have repercussions on the oral cavity. The objective of the study was to determine the biochemical manifestations and salivary biomarker alterations in the oral cavity resulting from cystic fibrosis or chronic consumption of drugs for the treatment of CF. We selected a total of five people with cystic fibrosis and four healthy people, from the city of Concepcion in the eighth region of Chile. Salivary pH, buffer capacity, total protein concentration, stimulated salivary flow rate and the presence of certain salivary enzymes were measured in patients suffering from the disease. It was observed that the salivary pH in subjects with cystic fibrosis tends to be higher than the reference values, the salivary flow rate and buffer capacity are less than normal, the total protein concentration in saliva is equal to the reference values and the presence of salivary biomarkers was determined through the electrophoresis technique. Cystic fibrosis affects those who suffer the disease in many ways, it generates changes at the salivary biomarker level, as well as in the oral cavity. The dentist must therefore, be able to identify these changes in order to treat them in the best possible approach for all types of patients.

Humans , Male , Female , Child , Adolescent , Adult , Interleukin-8/metabolism , Matrix Metalloproteinase 9/metabolism , Cystic Fibrosis/physiopathology , Cystic Fibrosis/metabolism , Vascular Endothelial Growth Factor A/metabolism , Epidermal Growth Factor/metabolism , Chemokine CXCL10/metabolism , Saliva/chemistry , Biomarkers/metabolism , Proteins , Chile , Electrophoresis , Hydrogen-Ion Concentration , Informed Consent
Mem. Inst. Oswaldo Cruz ; 113(6): e170542, 2018. tab, graf
Article in English | LILACS | ID: biblio-894932


BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.

Humans , Chemokine CXCL10/blood , Zika Virus Infection/complications , Gene Expression , Chemokines/immunology , Zika Virus Infection/immunology
Neuroscience Bulletin ; (6): 54-63, 2018.
Article in English | WPRIM | ID: wpr-777080


Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

Acetamides , Therapeutic Uses , Animals , Chemokine CXCL10 , Metabolism , Chloroquine , Toxicity , Chronic Disease , Cyclopropanes , Dehydration , Dinitrofluorobenzene , Disease Models, Animal , Formaldehyde , Toxicity , Freund's Adjuvant , Toxicity , Mice , Mice, Inbred C57BL , Mice, Knockout , Motor Activity , Pain , Pruritus , Pathology , Pyrimidines , Therapeutic Uses , Receptors, CXCR3 , Genetics , Metabolism , Skin , Pathology , Spinal Cord , Metabolism , Pathology , Time Factors , p-Methoxy-N-methylphenethylamine , Toxicity
Braz. j. otorhinolaryngol. (Impr.) ; 83(6): 670-676, Nov.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-889318


Abstract Introduction: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. Objective: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. Methods: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package. Using the BiNGO plugin in Cytoscape and pathway enrichment analysis in the PGS package, functional and pathway enrichment analyses were performed separately to predict potential functions of the differentially expressed genes. Furthermore, Transcription factor-differentially expressed gene pairs were searched, and then the transcription factor-differentially expressed gene regulatory network was visualized using Cytoscape software. Results: A total of 487 genes were screened as differentially expressed genes between the nasopharyngeal carcinoma samples and the normal nasopharyngeal tissue samples. Enrichment analysis indicated that PTGS2 was involved in the regulation of biological process and small cell lung cancer. ZIC2 and OVOL1 may function in nasopharyngeal carcinoma through targeting significantly up-regulated genes (such as PTGS2, FN1, CXCL9 and CXCL10) in the Transcription factor-differentially expressed gene regulatory network (e.g., ZIC2→PTGS2 and OVOL1→CXCL10). Conclusion: PTGS2, FN1, CXCL9, CXCL10, ZIC2 and OVOL1 might play roles in nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo é o câncer mais comum originário da nasofaringe. Objetivo: Estudar os mecanismos do câncer de nasofaringe; dados do microarray GSE12452 foram analisados. Método: GSE12452 foi obtido da base de dados Gene Expression Omnibus e inclui 31 amostras de carcinoma nasofaríngeo e 10 amostras de tecido nasofaríngeo normal. Os genes diferencialmente expressos foram analisados por ANOVA no kit PGS. Usando o plugin BiNGO no Cytoscape e análise de enriquecimento da via no kit PGS, análises de enriquecimento funcional e da via foram realizadas separadamente para prever as potenciais funções dos genes diferencialmente expressos. Além disso, os pares Fator de Transcrição - genes diferencialmente expressos foram pesquisados e em seguida a sua rede reguladora foi visualizada usando o programa Cytoscape. Resultados: Um total de 487 genes foram analisados como genes diferencialmente expressos entre as amostras de carcinoma nasofaríngeo e amostras de tecido nasofaríngeo normal. A análise de enriquecimento indicou que PTGS2 estava envolvido na regulação do processo biológico e câncer pulmonar de pequenas células. ZIC2 e OVOL1 podem funcionar no carcinoma nasofaríngeo almejando-se de maneira significativa os genes suprarregulados (como o PTGS2, FN1, CXCL9 e CXCL10) na rede reguladora de fator de transcrição - genes diferencialmente expressos (p.ex., ZIC2→PTGS2 e OVOL1→CXCL10). Conclusão: PTGS2, FN1, CXCL9, CXCL10, ZIC2 e OVOL1 podem desempenhar alguns papéis no carcinoma de nasofaringe.

Humans , Carcinoma/genetics , Gene Expression , Nasopharyngeal Neoplasms/genetics , Transcription Factors/genetics , Nuclear Proteins/genetics , Carcinoma/pathology , Cluster Analysis , Down-Regulation , Up-Regulation , Nasopharyngeal Neoplasms/pathology , Analysis of Variance , Gene Expression Profiling , Databases, Genetic , Microarray Analysis , Gene Regulatory Networks , Chemokine CXCL9/genetics , Chemokine CXCL10/genetics , Nasopharyngeal Carcinoma
Mem. Inst. Oswaldo Cruz ; 112(8): 561-568, Aug. 2017. graf
Article in English | LILACS | ID: biblio-894865


BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL.

Animals , Male , Mice , Organ Size/physiology , Interleukin-4/biosynthesis , Interleukin-10/biosynthesis , Leishmania infantum , Chemokine CXCL10/therapeutic use , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/drug therapy , Liver/pathology , Macrophages/drug effects , Cytokines/immunology , Interferon-gamma/analysis , Mice, Inbred BALB C
Braz. j. infect. dis ; 21(1): 42-50, Jan.-Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-839183


Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.

Humans , Adult , HIV Infections/drug therapy , HIV-1/drug effects , Antiretroviral Therapy, Highly Active , Macrophages/drug effects , CD4-Positive T-Lymphocytes/drug effects , Case-Control Studies , HIV Infections/blood , Acute Disease , Chronic Disease , Interleukins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Treatment Outcome , CD4-CD8 Ratio , Statistics, Nonparametric , CD8-Positive T-Lymphocytes/drug effects , Chemokine CCL5/metabolism , Lipopolysaccharide Receptors/drug effects , Viral Load/drug effects , Chemokine CXCL10/metabolism
Article in English | WPRIM | ID: wpr-222891


The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-κB pathway, via activation of the NF-κB transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of IκBα suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-κB signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrow-derived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-κB signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells.

Animals , Breast Neoplasms , Breast , Cell Line , Cell Movement , Chemokine CXCL10 , Coculture Techniques , Culture Media, Conditioned , Down-Regulation , Macrophages , Mice , Models, Animal , Neoplasm Metastasis , Osteoblasts , Osteoclasts
Article in Korean | WPRIM | ID: wpr-108728


PURPOSE: Recent studies have shown that interferon-gamma-inducible protein of 10 kDa (IP-10/CXCL10) levels is increased in acute bronchiolitis and asthma. The aim of this study was to examine the levels of IP-10 in children with wheezing and whether it correlates with other clinical variables. METHODS: A total of 62 subjects children were hospitalized for lower respiratory tract infection with wheezing and visited the Emergency Department due to an acute exacerbation of asthma. IP-10 levels were measured using enzyme-linked immunosorbent assay in the serum collected at admission. Serum IP-10 levels were evaluated for the relationships with age, sex, blood eosinophils counts, acute phase reactant, allergic sensitization, history of wheezing, and chest X-ray findings. RESULTS: Age showed a significant negative correlation with serum IP-10 levels (P=0.002). The serum levels of IP-10 were also significantly increased in patients with pneumonic infiltration on X-rays compared to those with normal or hyperinflation (P<0.009). There was no significant difference in the serum IP-10 level according to the other factors, including allergic sensitization. CONCLUSION: Serum IP-10 is significantly associated with inflammation of the lung and age, but not with allergic inflammation.

Asthma , Bronchiolitis , Chemokine CXCL10 , Child , Emergency Service, Hospital , Enzyme-Linked Immunosorbent Assay , Eosinophils , Humans , Inflammation , Lung , Respiratory Sounds , Respiratory Tract Infections , Thorax
Article in Chinese | WPRIM | ID: wpr-814961


OBJECTIVE@#To explore the effect of chronic intermittent hypoxia (CIH) on liver injury and to examine the expression of liver CXC chemokine ligand-10 (CXCL10) in the rats, and to explore the effect of N-acetylcysteine (NAC).
@*METHODS@#A total of 21 male SD rats were randomly divided into a control group, a CIH group and a CIH+NAC group (n=7 in each group). The control group exposed to normal gaseous environment, the other 2 groups were exposed to CIH for 5 weeks (8 h/d); the control group and the CIH group were given daily saline lavage, the CIH+NAC group daily received NAC solution. After the end of 5 weeks, the rats were killed, and the MDA content and SOD activity in rat liver tissues were detected. The liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of CXCL10 in the liver tissues was detected by immunohistochemical method.
@*RESULTS@#Compared with the control group, the MDA levels in rat liver tissues were increased (P<0.05), and the SOD levels were decreased (P<0.05) in the CIH group and the CIH+NAC group. Compared with the CIH group, the SOD levels in the rat liver tissues were increased (P<0.05), and the MDA levels were decreased in the CIH+NAC group. Compared with the control group, the hepatic steatosis and inflammatory reactions were more severe in the CIH group and the CIH+NAC group (both P<0.01). Compared with the CIH group, the hepatic steatosis and inflammatory reactions were reduced in the CIH+NAC group (P<0.05). The liver damage in the CIH+NAC group was less than that in the CIH group (P<0.05). Compared with the control group, the CXCL10 expression in the CIH group and the CIH+NAC group was increased (both P<0.01). The CXCL10 expression in the CIH+NAC group was down-regulated compared with that in the CIH group (P<0.01).
@*CONCLUSION@#CIH can lead to liver injury and induce CXCL10 expression in rat liver tissues. The NAC can alleviate rat liver oxidative stress and inflammation caused by CIH, and in turn to improve the liver injury in rats.

Acetylcysteine , Animals , Chemokine CXCL10 , Fatty Liver , Hypoxia , Inflammation , Male , Oxidative Stress , Rats , Rats, Sprague-Dawley
Article in English | WPRIM | ID: wpr-159288


PURPOSE: Immunotherapy is one of the treatment strategies for breast cancer, the most common cancer in women worldwide. In this approach, the patient's immune system is stimulated to attack microscopic tumors and control metastasis. Here, we used interferon γ-induced protein 10 (IP-10), which induces and strengthens antitumor immunity, as an immunotherapeutic agent. We employed Leishmania tarentolae, a nonpathogenic lizard parasite that lacks the ability to persist in mammalian macrophages, was used as a live delivery system for carrying the immunotherapeutic agent. It has been already shown that arginase activity, and consequently, polyamine production, are associated with tumor progression. METHODS: A live delivery system was constructed by stable transfection of pLEXSY plasmid containing the IP-10-enhanced green fluorescent protein (IP-10-egfp) fusion gene into L. tarentolae. Then, the presence of the IP-10-egfp gene and the accurate integration location into the parasite genome were confirmed. The therapeutic efficacy of IP-10 delivered via L. tarentolae and recombinant pcDNA-(IP-10-egfp) plasmid was compared by determining the arginase activity in a mouse 4T1 breast cancer model. RESULTS: The pcDNA-(IP-10-egfp) group showed a significant reduction in tumor weight and growth. Histological evaluation also revealed that only this group demonstrated inhibition of metastasis to the lung tissue. The arginase activity in the tissue of the pcDNA-(IP-10-egfp) mice significantly decreased in comparison with that in normal mice. No significant difference was observed in arginase activity in the sera of mice receiving other therapeutic strategies. CONCLUSION: Our data indicates that IP-10 immunotherapy is a promising strategy for breast cancer treatment, as shown in the 4T1-implanted BALB/c mouse model. However, the L. tarentolae-(IP-10-EGFP) live delivery system requires dose modifications to achieve efficacy in the applied regimen (six injections in 3 weeks). Our results indicate that the arginase assay could be a good biomarker to differentiate tumoral tissues from the normal ones.

Animals , Arginase , Breast Neoplasms , Chemokine CXCL10 , Female , Genetic Therapy , Genome , Humans , Immune System , Immunotherapy , Interferons , Leishmania , Lizards , Lung , Macrophages , Mice , Neoplasm Metastasis , Parasites , Plasmids , Transfection , Tumor Burden
Egyptian Journal of Hospital Medicine [The]. 2015; 61 (October): 389-405
in English | IMEMR | ID: emr-173897


Background: The development of effective tools for the large-scale analysis of gene expression has provided new insights into the involvement of gene networks and regular pathways in various disease processes. The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follow: CXCL9 [Mig], CXCL10 [IP-10] and CXCL11 [I- TAC], and play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. Aim of the work: The study is a logical functional approach for the development of serum markers chemokines that bind to CXC chemokine receptor 3 to determine whether they play a role in the future of immune system to clear HCV, these chemokines: CXCL9, CXCL10 and CXCL11

Patients and methods: 131 male and female patients with chronic hepatitis C virus [CHCV] infection, their age ranges between 22 and 55 years,selected from the National Hepatology and Tropical Medicine Research Institute. The included patients were divided to two groups, the first group: 80 patients were investigated for the predictive values of CXCL9,10,11 and CXCR3 chemokines in peripheral blood mononuclear cells [PBMCs], the second group were fifty one patients analyzed for the expression of surface markers on CD8+T cells. Twenty healthy individuals were included to serve as controls for each group. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation and serological assay

Results: Chemokine CXCL9, CXCL10, CXCL11 and their receptor CXCR3 expression levels are induced in PBMCs during CHCV infection, associated with increased the expression levels of CD8+T cells in CHCV patients

Conclusion: The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection

Recommendations: The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver, the blocking of chemokines and chemokine receptor engagement is a therapeutic strategy that should be explored in the near future for non-responders to current anti-HCV therapy

Humans , Male , Female , Adult , Middle Aged , Chemokine CXCL9 , Chemokine CXCL10 , Chemokine CXCL11 , Receptors, CXCR3 , Up-Regulation , Genes , Chemokines , Immune System
Article in Chinese | WPRIM | ID: wpr-346193


<p><b>OBJECTIVE</b>To study the roles of chemokine receptor 3 (CXCR3) on lymphocytes and interferon-γ-inducible protein-10 (IP-10) of peripheral blood in childhood bronchiolitis.</p><p><b>METHODS</b>Fifty-five children with bronchiolitis were classified into Group I (with allergic factors) and Group II (without allergic factors). Twenty-eight children with noninfectious diseases were enrolled randomly as the control group. The expression of CXCR3 (CD183 as its molecular marker) on lymphocytes of peripheral blood was detected by flow cytometry. Serum IP-10 level was measured using ELISA.</p><p><b>RESULTS</b>The expression of CD183(+) cells on CD4(+) and CD8(+) lymphocytes in peripheral blood in children with bronchiolitis from both Group I and Group II was significantly higher than that in the control group (P<0.05), and Group I had higher expression of CD183(+) cells on CD4(+) and CD8(+) lymphocytes than Group II (P<0.05).Serum IP-10 levels in Group I and Group II were significantly higher than those in the control group (P<0.05). However, there was no significant difference in serum IP-10 levels between Group I and Group II.</p><p><b>CONCLUSIONS</b>CXCR3 and IP-10 are involved in the pathogenesis of bronchiolitis, and CXCR3 is associated with allergic factors.</p>

Bronchiolitis , Allergy and Immunology , Chemokine CXCL10 , Blood , Physiology , Child, Preschool , Female , Humans , Infant , Lymphocytes , Allergy and Immunology , Male , Receptors, CXCR3 , Blood , Physiology
AJMB-Avicenna Journal of Medical Biotechnology. 2014; 6 (1): 27-37
in English | IMEMR | ID: emr-141726


Mesenchymal Stem Cells [MSCs] are recently introduced as novel immunological gene carriers for treatment of cancer. It is believed that balance between the expression of angiogenic and anti-angiogenic factors, such as SDF-1 and IP-10, may regulate neovascularization within the tumor. In this study, we compared the expression of important tumor promoting mediators in IP-10-transfected Adipose Derived Stem Cells [ASCs] to those transfected with SDF-1. ASCs were isolated from adipose tissue of a normal subject undergoing cosmetic mamoplasty surgery using collagenase. ASCs were transfected with IP-10 or SDF-1 propagated plasmids by electroporation method and Lipofectamin 2000. Expressions of SDF-1, CXCR4, IP-10, Bcl-2, MMP2, IL-10, IGF-1, and VEGF were detected in transfected ASCs using quantitative Real-Time Polymerase Chain Reaction [qRT-PCR]. Results showed that the expressions of SDF-1, CXCR4, Bcl-2, MMP2, IL-10, IGF-1, and VEGF were upregulated in SDF-1-transfected ASCs. In contrast, Bcl-2 and MMP2 transcripts showed 45×103 and 10 fold lower expression in ASCs transfected with IP-10 compared to non-transfected cells. Anti-angiogenic chemokines such as IP-10 may modulate tumor promoting properties of ASCs and would be introduced as novel candidates for tumor immunotherapy; however, further studies are needed to be conducted

Humans , Down-Regulation , Matrix Metalloproteinase 2 , Proto-Oncogene Proteins c-bcl-2 , Adipose Tissue , Transfection , Chemokine CXCL10 , Chemokine CXCL12 , Immunotherapy
Article in English | WPRIM | ID: wpr-39641


The aim of the present study was to identify a new candidate anti-inflammatory compound for use in the active stage of thyroid-associated ophthalmopathy (TAO). Benzylideneacetophenone compound JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] was synthesized based on a structural modification of yakuchinone B, a constituent of the seeds of Alpinia oxyphylla, which belongs to the ginger family (Zingiberaceae), has been widely used in folk medicine as an anti-inflammatory phytochemical. Orbital fibroblasts were primarily cultured from patients with TAO, and the potential of JC3 to suppress the interferon (IFN)-gamma-induced protein (IP)-10/CXCL10 production in these cells was determined. IFN-gamma strongly increased the level of IP-10/CXCL10 in orbital fibroblasts from patients with TAO. JC3 exerted a significant inhibitory effect on the IFN-gamma-induced increase in IP-10/CXCL10 in a dose-dependent manner; its potency was greater than that of an identical concentration of yakuchinone B with no toxicity to cells at the concentration range used. Moreover, the constructed dimer and trimer polystructures of JC3, showed greater potency than JC3 in suppressing the IFN-gamma-induced production of IP-10/CXCL10. JC3 significantly attenuated the IP-10/CXCL10 mRNA expression induced by IFN-gamma, and a gel-shift assay showed that JC3 suppressed IFN-gamma-induced DNA binding of signal transducer and activator of transcription-1 (STAT-1) in TAO orbital fibroblasts. Our results provide initial evidence that the JC3 compound reduces the levels of IP-10/CXCL10 protein and mRNA induced by IFN-gamma in orbital fibroblasts of TAO patients. Therefore, JC3 might be considered as a future candidate for therapeutic application in TAO that exerts its effects by modulating the pathogenic mechanisms in orbital fibroblasts.

Cells, Cultured , Chalcone/chemical synthesis , Chemokine CXCL10/genetics , Diarylheptanoids/chemistry , Fibroblasts/drug effects , Graves Ophthalmopathy/metabolism , Humans , Interferon-gamma/metabolism , Orbit/cytology , RNA, Messenger/genetics , STAT1 Transcription Factor/genetics
IJM-Iranian Journal of Microbiology. 2013; 25 (1): 28-35
in English | IMEMR | ID: emr-143250


Alterations in CXCL10 [a Th1 chemokine] expression have been associated with various diseases. The aim of this study was to evaluate the serum CXCL10 levels in H. pylori- infected patients with peptic ulcer [PU], H. pylori- infected asymptomatic [AS] subjects and healthy H. pylori-negative subjects, and also to determine its association with bacterial virulence factor cytotoxin-associated gene A [CagA]. Serum samples from 90 H. pylori infected patients with PU [70 were anti-CagA[+], 20 were anti-CagA[-]], 65 AS carriers [40 were anti-CagA[+], 25 were anti-CagA[-]] and 30 healthy H. pylori-negative subjects [as a control Group] were tested for concentrations of CXCL 10 by using the ELISA method. The mean serum levels of CXCL10 in PU patients [96.64 +/- 20.85 pg/mL] were significantly lower than those observed in AS subjects [162.16 +/- 53.31 pg/mL, P < 0.01] and the control group [193.93 +/- 42.14 pg/mL, P < 0.02]. In the PU group, the serum levels of CXCL10 in anti-CagA[+] subjects was significantly higher in comparison to anti-CagA[-] patients [P < 0.04]. These results showed that the mean concentrations of CXCL10 in H. pylori-infected-PU patients was lower than AS carriers and control group. In the PU group, the serum levels of CXCL10 were associated with bacterial factor CagA

Humans , Male , Female , Helicobacter Infections , Chemokine CXCL10 , Peptic Ulcer , Antigens, Bacterial , Bacterial Proteins , Virulence Factors
IJI-Iranian Journal of Immunology. 2013; 10 (1): 40-46
in English | IMEMR | ID: emr-142676


Alopecia Areata [AA] is a non-scarring, autoimmune disorder which causes hair loss. Inflammatory reactions are involved in hair loss of the scalp and/or body. The involvement of chemokine receptors in the pathogenesis of AA is well defined among which, CXCL1 acts on neutrophils and CXCL9, CXCL10 and CXCL12 and serve as T lymphocytes recruiters. To study the serum levels of ELR+ and ELR- CXCL1, CXCL9, CXCL10 and CXCL12 in the patients suffering from AA and healthy controls. The study population of consisted of 30 patients suffering from AA and 30 healthy controls. Serum concentrations of CXCL1, CXCL9, CXCL10 and CXCL12 were measured using enzymelinked immunosorbent assay [ELISA]. Current results showed that AA patients had significantly elevated serum levels of CXCL9 and CXCL10 in comparison to controls [p<0.001]. These results also demonstrated that serum levels of CXCL1 and CXCL12 were significantly decreased in AA patients compared to control [p<0.001]. CXCL9 and CXCL10 are elevated in the AA patients and may be involved in the recruitment of T lymphocytes to the inflamed tissues. Moreover, due to the significant role played by these chemokines in angiogenesis/ angiostatis phenomenon they could be considered as useful biomarkers in AA diagnosis and therapy

Humans , Male , Female , Chemokine CXCL1/blood , Chemokine CXCL10/blood , Chemokine CXCL12/blood , Chemokine CXCL9/blood , Receptors, Chemokine , Enzyme-Linked Immunosorbent Assay , Biomarkers
Article in English | WPRIM | ID: wpr-343123


The expression profile in the mouse hepatitis B virus X (HBx)-transfected model was investigated in order to lay a foundation for further study on the implication of cytokines expression in hepatitis B virus (HBV) infection. Hydrodynamic injection method via the tail vein was used to establish the animal HBx-transfected model. By using microassay, the differential expression of gene in each group was analyzed, which was further confirmed by using real-time PCR and semi-quantitative PCR. Most of chemokine genes such as Ccl2, Ccl5, Ccl9, MIG and IP-10 were up-regulated in the HBx-transfected mouse model versus the control mice, which was coincided with the microarray results. Western blotting and immunohistochemistry were applied to detect the expression of MIG and IP-10 in the liver tissues. Simultaneously, ELISA was adopted to measure the content of IFN-γ in the liver tissues. DNA microassay revealed that the expression of 611 genes changed in HBx-transfected mice as compared with that in pCMV-tag2B-transfected mice, and most of the screened chemokines were up-regulated (including MIG and IP-10). Additionally, IFN-γ protein levels were increased by 20.7% (P<0.05) in pCMV-tag2B-HBx-transfected mice as compared with the untreated mice. IFN-γ protein levels were reduced by 53.9% (P<0.05) in pCMV-tag2B-transfected mice as compared with the untreated mice, which was consistent with the up-regulation of MIG and IP-10. It was suggested HBx transfection could induce the expression of MIG and IP-10 in the liver tissues, which might play the roles in HBV-related liver immunity and cytokines-mediated antiviral effect.

Animals , Chemokine CXCL10 , Allergy and Immunology , Chemokine CXCL9 , Allergy and Immunology , Cytokines , Allergy and Immunology , DNA, Viral , Genetics , Hepatitis B , Genetics , Allergy and Immunology , Virology , Hepatitis B virus , Genetics , Allergy and Immunology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Trans-Activators , Genetics , Transfection , Methods