Therapeutic Effect of Ziziphi Spinosae Semen-Albiziae Flos on Depression in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain，NOD-like receptor thermal protein domain associated protein 1 （NLRP1）/chemokine ligand 1 （CXCL1）/chemokine receptor 2 （CXCR2） pathway in the hippocampus of the rat model of chronic unpredictable mild stress （CUMS）-induced depression. MethodA total of 120 male SD rats were randomized into blank，CUMS，CUMS + low-，medium-，and high-dose （4，8，16 g·kg-1） Ziziphi Spinosae Semen-Albiziae Flos，and CUMS + venlafaxine hydrochloride （0.008 g·kg-1） groups，with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test，tail suspension test，forced swimming test，and Morris water maze test.Quantitative real-time PCR （Real-time PCR） and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α （TNF-α），interleukin （IL）-18，IL-1β，and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species （ROS） in the hippocampus. ResultCompared with the blank group，the CUMS group showed decreased preference to sugar water and times of crossing the platform （P<0.01），and increased immobility time of tail suspension，forced swimming floating time，and escape latency （P<0.01）.Compared with the CUMS group，the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats （P<0.05，P<0.01）.Compared with the blank group，the CUMS group showed up-regulated protein levels of NLRP1，CXCL1，and CXCR2 （P<0.01） and elevated levels of IL-18，IL-1β，TNF-α，and IL-6 （P<0.01） in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride attenuated the activation of NLRP1/CXCL1/CXCR2 signaling pathway and lowered the levels of inflammatory cytokines in the hippocampus of CUMS rats （P<0.05，P<0.01）.In addition，Ziziphi Spinosae Semen-Albiziae Flos lowered the level of ROS in the hippocampus （P<0.05，P<0.01）. ConclusionZiziphi Spinosae Semen-Albiziae Flos can mitigate the depressive behaviors of the rat model of CUMS-induced depression by inhibiting the activation of NLRP1/CXCL1/CXCR2 signaling pathway.

Relationship between expression of chemokine receptor 2 and basic fibroblast growth factor in aqueous humor and prognosis of trabeculectomy in patients with acute primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the relationship between the levels of chemokine receptor 2(CXCR2)and basic fibroblast growth factor(bFGF)in aqueous humor and the prognosis of trabeculectomy in patients with acute primary angle-closure glaucoma(APACG).METHODS: A total of 80 cases(80 eyes)APACG patients who underwent trabeculectomy in our hospital from June 2020 to January 2022 were collected in the case group. According to the postoperative efficacy, they were grouped into a success group of 60 cases(60 eyes)and a failure group of 20 cases(20 eyes). Another 86 cataract patients(86 eyes)who underwent phacoemulsification with normal intraocular pressure in our hospital during the same period were included in the control group. Enzyme linked immunosorbent assay was applied to detect the levels of CXCR2 and bFGF in aqueous humor. ROC curve was applied to analyze the value of predicting trabeculectomy failure in APACG patients by the levels of CXCR2 and bFGF in aqueous humor. Furthermore, multivariate Logistic regression was applied to analyze the influencing factors of trabeculectomy failure in APACG patients.RESULTS: The levels of CXCR2 and bFGF in the aqueous humor of the case group were significantly higher than those of the control group(P&#x003C;0.05). The levels of CXCR2 and bFGF in the aqueous humor of the failed group and the proportion of patients with postoperative shallow anterior chamber were significantly higher than those of the successful group(P&#x003C;0.05). The AUC for predicting trabeculectomy failure in APACG patients using CXCR2 and bFGF levels alone and in combination was 0.885, 0.883 and 0.953, respectively. CXCR2 and bFGF were independent risk factors for trabeculectomy failure in APACG patients(P&#x003C;0.05).CONCLUSION: The levels of CXCR2 and bFGF in the aqueous humor of APACG patients are obviously elevated, and both are risk factors for trabeculectomy failure.

Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice

ABSTRACT Purpose To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2). Methods Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1β and TNF-α. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining. Results We found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1β and TNF-α, which were then partly abolished by SB225002. Conclusions CXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.

Mutations in foregut SOX2 cells induce efficient proliferation via CXCR2 pathway

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

Expressions and clinical significance of CXC chemokine receptor 1 and 2 and CXCL8 in hepatitis B related hepatocellular carcinoma / 中国免疫学杂志

Objective:To investigate the expression levels of CXCR1,CXCR2 and their common ligand CXCL8 in peripheral blood mononuclear cells (PBMCs) and liver biopsy from the patients with hepatitis B related hepatocellular carcinoma and their clinical significances.Methods:Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the mRNA levels of CXCR1,CXCR2,CXCL8 in the peripheral blood mononuclear cells of thirty-six hepatitis B related hepatocellular carcinoma and the protein levels of CXCR1 and CXCR2 and CXCL8 in liver biopsy were detected by SP immunohistochemical method.The level of C-reactive protein in serum was determined by chemiluminescence immunoassay respectively.Then,the correlations between CRP and the mRNA of CXCR1,CXCR2 and CXCL8 were analyzed.Results:The mRNA levels of CXCR1 (0.952 7±0.197 2),CXCR2 (0.896 9±0.173 0),CXCL8 (1.771 9±0.248 9) in the PBMCs of hepatitis B related hepatocellular carcinoma were significantly higher than those in controls (P＜0.01).And the protein levels of CXCR1,CXCR2 and CXCL8 were also obviously increased in liver biopsy of hepatitis B related hepatocellular carcinoma (P＜0.05).In addition,there was positive correlations between the level of serum C-reactive protein and the mRNA expression of CXCR1 (r =0.54,P＜0.01),CXCR2 (r =0.49,P＜0.01),CXCL8 (r =0.63,P＜0.01).Conclusion:The levels of CXCR1,CXCR2 and CXCL8 significantly increased in hepatitis B related hepatocellular carcinoma patients and positively correlated with serum CRP,suggesting that CXCR1,CXCR2 and their common ligand CXCL8 signal transduction process may play a key role in the pathological process of hepatitis B related hepatocellular carcinoma,which may provide a new direction for the immune intervention therapy of hepatocellular carcinoma.

Expression and Clinical Significance of CXCR1 and CXCR2 in Triple-negative Breast Cancer / 中国医科大学学报

Objective To investigate the expression of CXC chemokine receptor 1 (CXCR1) and CXC chemokine receptor 2 (CXCR2) in triplenegative breast cancer (TNBC) and its significance.Methods The EnVision immunohistochemistry system was used to detect the expression of CXCR1 and CXCR2 in 28 specimens from normal tissues adjacent to breast cancer,30 specimens of invasive ductal carcinoma not otherwise specified (IDC-NOS),and 34 TNBC specimens.The relationship between the expression of CXCR1 and CXCR2,and clinical pathological features was analyzed.Results In the adjacent normal tissues of breast cancer,the positive expression rates of CXCR 1 and CXCR2 were 89.3％ and 92.9％,respectively;CXCR1 and CXCR2 expression displayed no significant association with clinicopathological parameters such as age,tumor size,or Scarff-Bloom-Richardson (SBR) score.The positive expression rates of CXCR1 and CXCR2 were 63.3％ and 60.0％,respectively,in the IDC-NOS samples and 23.5％ and 35.3％,respectively,in the TNBC samples.There was a positive correlation between CXCR1 and CXCR2 expression in the TNBC samples (r =0.606,P ＜ 0.001).Conclusion Correlation of CXCR1 and CXCR2 expression with sample type was strong in adjacent normal tissues,moderate in IDC-NOS samples,and low in TNBC samples.CXCR1 expression was positively correlated with CXCR2 expression in all sample types.The expression of CXCR1 or CXCR2 was closely related to the development and promotion of TNBC.

Study on protective effect of astragaloside Ⅳ in septic mice / 中国药理学通报

Aim To study the effect of astragaloside (AS-Ⅳ) in CLP-induced septic mice.Methods C57BL/6 mice were randomly divided into the sham group, CLP group and CLP+ AS-Ⅳ group.Two days before operation, AS-Ⅳ (10 mg·kg-1) solution was intragastrically administered into CLP +AS-Ⅳ group, and the other groups were treated with normal saline.A sepsis model was established by cecal ligation and puncture (CLP).Blood, peritoneal fluid and tissue organs were collected at 6 h and 24 h.Neutrophils of blood were purified by Percoll density gradient.Transwell was used to detect the chemotaxis function of neutrophils.The killing activity of neutrophils was detected by coculture with E.coli.Results The survival rate of AS-Ⅳ-pretreated septic mice significantly increased.The number of neutrophils in peritoneal fluid was enhanced markedly.The number of bacteria in the peritoneal fluid, blood and tissue organs such as liver, lung and kidney significantly decreased after AS-Ⅳ pretreatment.The chemotaxis and killing activity of neutrophils increased significantly in AS-Ⅳ-treated mice (P<0.05).Conclusion Astragaloside displays an immunoprotective effect in CLP-induced septic mice, which is related to the upregulation of CXCR2 expression on neutrophils and the increase of neutrophil antibacterial activity.

Expression and clinical significance of CXC chemokine receptors 1 and 2 and CXCL8 in primary hepatocellular carcinoma / 中华微生物学和免疫学杂志

Objective To investigate the expression and clinical significance of CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2) and CXCL8 in peripheral blood mononuclear cells (PBMCs) and liver biopsy tissues from patients with primary hepatocellular carcinoma (PHC).Methods Serum specimens were collected from 36 patients with PHC, 30 patients with liver cirrhosis and 28 healthy subjects.Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs.Streptavidin-perosidase (SP) immunohistochemistry was used to detect the expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues.Levels of C-reactive protein (CRP), alpha-fetoprotein (AFP) and ferritin (FER) in the serum specimens were detected by chemiluminescence immunoassay.Then the correlations between these markers were analyzed.Results All of the results showed that the expression of CXCR1, CXCR2 and CXCL8 at mRNA level in PBMCs from the PHC group were higher than those of the healthy control group (P<0.01) as well as those of the liver cirrhosis group (P<0.05).Up-regulated expression of CXCR1, CXCR2 and CXCL8 in patients with PHC were associated with the depth of tumor invasion, lymph node or distant metastasis, clinical stage and levels of CRP, AFP and FER in serum (P<0.05).The expression of CXCR1, CXCR2 and CXCL8 at protein level in liver biopsy tissues were also significantly increased in the PHC group in comparison with those of the healthy control group as indicated by the result of SP immunohistochemistry (P<0.05).Conclusion Levels of CXCR1, CXCR2 and CXCL8 in the patients with PHC are significantly increased and positively correlated with the levels of AFP, FER and CRP in serum, suggesting that the signal transduction process mediated by CXCR1, CXCR2 and their common ligand CXCL8 may play a key role in the pathological process of PHC.This study may provide a potential new strategy for immune intervention in hepatocellular cancer.

Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment / Caracterização de marcadores inflamatórios associados a pacientes com lúpus eritematoso sistêmico em tratamento

ABSTRACT Objective: To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Patients and methods: Peripheral venous blood was collected from systemic lupus erythematosus patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cytokines were assayed in serum samples. Purified neutrophils were assayed by their ability to phagocytize human plasma-opsonized zymosan. Results: Patients had a median (interquartile range) disease activity index of 1.0 (0-2.0) characteristic of patients in remission. Interleukin-6 and interleukin-10 serum concentrations were significantly higher in the patient group compared to controls and the phagocytic index of circulating neutrophils was significantly reduced in patients compared to controls. The levels of interleukin-2, interleukin-5, interleukin-8 and tumor necrosis factor alpha did not significantly differ between patients and controls. Flow cytometric analysis revealed that the integrin expression levels were reduced in lymphocytes (but not in neutrophils) obtained from systemic lupus erythematosus patients, while surface expression of the chemokine receptor 2 was similar in both neutrophils and lymphocytes. Conclusion: Systemic lupus erythematosus patients receiving standard treatment presented with elevated systemic levels of interleukin-6 and interleukin-10, reduced neutrophil phagocytic capacity, and reduced lymphocyte expression of integrin even when symptoms were in remission. These alterations to innate immune components may put these individuals at a greater risk for acquiring infections.

RESUMO Objetivo: Caracterizar os perfis inflamatórios de pacientes com lúpus eritematoso sistêmico (LES) que recebiam o tratamento padrão em comparação com controles saudáveis. Pacientes e métodos: Coletou-se o sangue venoso periférico de pacientes com LES (n = 14) e controles (n = 18) no momento da entrada no estudo. As amostras de sangue foram usadas para quantificação, por citometria de fluxo, da expressão dos antígenos de superfície CD11b (integrina) e CXCR2 em neutrófilos e linfócitos, enquanto as citocinas foram avaliadas em amostras de soro. Avaliou-se a capacidade dos neutrófilos purificados de fagocitar zimosan opsonizado com plasma humano. Resultados: Os pacientes apresentavam uma pontuação mediana (intervalo interquartil) no Sledai de 1 (0-2), característica de pacientes em remissão. As concentrações séricas de IL-6 e IL-10 foram significativamente maiores no grupo de pacientes em comparação com os controles; o índice de fagocitose de neutrófilos circulantes estava significativamente reduzido nos pacientes em comparação com os controles. Os níveis de IL-2, IL-5, IL-8 e TNF-α não diferiram significativamente entre pacientes e controles. A análise da citometria de fluxo revelou que os níveis de expressão de CD11b estavam reduzidos nos linfócitos (mas não nos neutrófilos) obtidos de pacientes com LES, enquanto a expressão do receptor de superfície CXCR2 foi semelhante em neutrófilos e linfócitos. Conclusão: Os pacientes com LES que recebiam tratamento padrão apresentaram níveis sistêmicos elevados de IL-6 e IL-10, redução na capacidade fagocítica dos neutrófilos e redução da expressão de CD11b em linfócitos, mesmo quando os sintomas estavam em remissão. Essas alterações nos componentes da imunidade inata podem colocar esses indivíduos em maior risco de adquirir infecções.

Papel de receptores CXCR2 na mucosite intestinal induzida por Irinotecano

INTRODUÇÃO: O irinotecano é um antineoplásico usado no tratamento de primeira e segunda linha d o câncer colorretal . No entanto, um importante efeito colateral associado ao irinotecano, a mucosite intestinal, tem impactado negativamente n a qualidade de vida dos pacientes e n o sucesso terapêutico. Trabalhos anteriores demonstraram que na patogênese da mucosite intestinal há a participação de mediadores pró - inflamatórios, como IL - 1, IL - 18, IL - 33, óxido nítrico dentre outros, cuja modulação leva à redução do infiltrado neutrofílico no intestino e mel hora do dano tecidual. Entretanto, o papel de receptores de quimiocinas, como o CXCR2, importante s no recrutamento de neutrófilos, ainda não fo ram investigado s no contexto da mucosite. OBJETIVOS: Avaliar o papel d e receptores CXCR2 n a mucosite intestinal i nduzida p el o Irinotecano. MÉTODOS: Camundongos C57BL/6 machos, 18 - 25g, foram divididos em grupos (n=6), administrados por 4 dias com salina (5mL/kg, i.p) ou com irinotecano (75, 90, 105 ou 120 mg/kg, i.p). A dose de 120 mg/kg foi a que melhor reproduziu o quadro inflamatório característico da mucosite , sendo então utilizada nos ensaios posteriores em associação ao SB225002 , um antagonista de receptores CXCR2 . Os animais foram analisados quanto ao peso corpóreo , escores de diarreia, contagem de leucócitos. A pós a eutanásia, uma amostra de intestino foi coletada para análise histopatológica e morfométrica, dosagem de mieloperoxidase e níveis de IL - 1β , IFN - γ e KC . Além disso, o comprimento do intestino delgado foi mensurado , bem como o peso do conteúdo sólido . Avaliou - se também a bacteremia. Adicionalmente, realizou - se a quantificação dos re ceptores CXCR2 e CCR2, além do ensaio de quimiotaxia in vitro de neutrófilos isolados de camundongos tratados com IRI ou com IRI+SB225002. (Protocolo CEPA 58/14)...

INTRODUCTION: Irinotecan is an anticancer agent used in first and second line treatment protocols for colorectal cancer. However, a major side effect associated with irinotecan, intestinal mucositis, has negatively impacted on patient’s quality of life and limiting the therapeutic outcome. The literature reports the involvement of several inflammatory mediators in the pathogenesis of intestinal mucositis, including IL - 1, IL - 18, IL - 33, nitric oxide and several others, whose pharmacological inhibition prevents neutrophil infiltration and leads to mucositis improvement. However, the role of chemokine receptors that are important to neutrophil recruitment, such as CXCR2, in intestinal mucositis is unknown. AIMS: To study the role of CXCR2 receptors in the pathogenesis of irinotecan - induced intestinal mucositis. METHODS: M ale C57BL /6 mice (n = 6) were divided into groups and injected with either saline (5ml / kg, ip) or irinotecan (75, 90, 105 or 120 mg/kg ip) for 4 days. The dose of 120 mg / kg reproduce d the inflammatory condition of mucositis, so it was used in association with SB225002, a CXCR2 antagonist. Body mass variation, diarrhea scores and leukocyte count were recorded. Following euthanasia, intestinal samples were collected for histopathological analysis, mieloperoxidase activity (MPO), IL - 1β, KC and IFN - γ levels. In addition, the length of the small intestine was measured so was the weight of its solid contents. Bacteremia was further carried out. Additionally, we measured the expression of CXCR2 and CCR2 receptors on neutrophils surface. We also performed the in vitro chemotaxis assay, using neutrophils isolated from bone marrow of mice treated with IRI or IRI + SB225002 (Study approval number: 58/14)...

The expressions of chemokine CXCL5 and its receptor CXCR2 in HCC and the significance in the prognostic evaluation / 实用医学杂志

Objective To detect the expressions of chemokine CXCL5 and its receptor CXCR2 in hepatocellular carcinoma (HCC), investigate their relationships between CXCL5, CXCR2 and clinicopathologic features and probe into the significance in the evaluation of prognosis. Methods Immunohistochemical Envision method was utilized to detect the expressions of CXCL5 and CXCR2 in HCC , to explore their relationship between CXCL5, CXCR2 and clinicopathologic features and MVD in HCC. Results (1) The high expression rates of CXCL5 and CXCR2 protein was 64.7% and 68.6%, respectively, significantly higher than those in adjacent tissues of HCC(17.6%, 15.7%, P < 0.05). The overexpression of CXCL5 protein had correlation with tumor size, differentiation, TNM stage and vascular invasion (P < 0.05) and the overexpression of CXCR2 protein did with tumor grade and vascular invasion (P < 0.05). (2) The value of MVD was higher in HCC than that in the adjacent tissues of HCC (P < 0.05), and had positive correlation with the expressions of CXCL5, and CXCR2 proteins. (3) The higher rates of recurrence and metastasis were in the groups of higher expression of CXCL5 and CXCR2 proteins (P < 0.05). Conclusions The overexpressions of CXCL5 and CXCR2 may promote the occurrence and development of HCC as well as the neovasculation in HCC. Therefore, they can be used as markers to evaluate the prognosis of HCC.

The role of CXCR2 in the invasion and metastasis of head and neck squamous cell carcinoma / 实用口腔医学杂志

Objective:To explore the role of CXCR2 in the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC).Methods:The expression of CXCR2 in HNSCC tissues of 105 cases was detected by immunohistochemical staining,the correlation between CXCR2 expression and cervical lymph node metastases of HNSCC was analysed.Then,3 stable HNSCC cell lines with CXCR2 interference were established,the effects of CXCR2 silencing on cell migration and invasion were observed by in vitro tests.Results:CXCR2 was positively expressed in 51.43% of HNSCC specimens and was statistically associated with the cervical lymph node metastases of HNSCC.CXCR2 silencing markedly inhibited the migration and invasion of HNSCC cells in vitro.Conclu-sion:CXCR2 may play a key role in the invasion and metastases of HNSCC.

Expression of CXCL8 and its receptors (CXCR1 and CXCR2) in peripheral blood neutrophils of chronic hepatitis B / 中国免疫学杂志

Objective:To study on the levels of CXCL8 and its receptors (CXCR1 and CXCR2) in peripheral blood neutrophils of the patients with chronic hepatitis B.Methods:The neutrophils were isolated and purified by neutrophil isolation medium,and the loads of HBV-DNA in neutrophils were detected by PCR,and the levels of HBeAg in serum were measured by ELISA.The patients were divided into different groups according to the detective results so that the expressions of CXCL8 and its receptors ( CXCR1,CXCR2) in neutrophils were detected by the methods of streptavidin-biotin complex ( SABC ) immunocytochemistry stain.Results:The data of SABC immunocytochemical stain showed that the positive color of CXCL8 was mainly located in the cytoplasm of PMNs.However,the most positive color of CXCR1and CXCR2 was mainly expressed in the cytoplasm and cell membrane.Interestingly,the deeper immune coloring of CXCL8 and CXCR1, and relatively shallow immune coloring of CXCR2 were explored in the group with positive of HBeAg.The similar detective results also had been found in the cases with positive of HBV DNA in neutrophils.Compared with the normal control group,the levels of CXCL8 and CXCR1 in the patients were significantly increased ( P0.05).Conclusion:After neutrophils occult infected by HBV,not only the secretion of CXCL8 can be promoted, but also the expression of CXCR1 will be further increased.The data of immunohistochemical staining have been shown that the color degree of CXCL8 and its receptors ( CXCR1, CXCR2 ) are positive correlation to the level of HBeAg and the loads of HBV DNA.More PMNs can be chemotactic attraction to lesion so as to participate in the local inflammatory injury and tissue repair via the interactive pathway of the high expression of CXCR1 on surface of neutrophils with CXCL8.

Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.

Expression and function of CXCR2, CXCR7 of acute leukemic cells in rat

OBJECTIVE@#To investigate the expression and function of chemokine receptor CXCR2 and CXCR7 in the rat with acute leukemia.@*METHODS@#Flow cytometry and RT-PCR were used to detect the CXCR2, CXCR7 expression on the bone marrow cell surface of the acute leukemia group and the control group.@*RESULTS@#The bone marrow cell surface CXCR2, CXCR7 relative fluorescence intensity of the observation group was significantly higher than the control group (P<0.05). The CXCR7 expression of the extramedullary infiltration group was significantly higher than non-extramedullary infiltration group (P<0.05). The CXCR2, CXCR7mRNA median expression level of the observation group was higher than the control group. The CXCR2 expression and CXCR7 expression of the observation group was positively correlated, and the correlation coefficient was 0.782 (P<0.01).@*CONCLUSIONS@#The chemokine receptor CXCR2 and CXCR7 are highly expressed in acute leukemia, which may be associated with the occurrence of leukemia.

Blockade of CXCR1/2 chemokine receptors protects against brain damage in ischemic stroke in mice

OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.

Study on CXCR1/CXCR2 antagonist G31P anti-inflammatory reaction mediated by neutrophils / 中华微生物学和免疫学杂志

Objective To Study on CXCR1/CXCR2 antagonist G31P anti-inflammatory reaction mediated by neutrophils.Methods Detect whether G31P can block chemotaxis of neutrophils induced by human IL-8 and inhibit the release of IL-8 by epithelia of segmental bronchus;establish HEK293 cell line transfected by pcDNA3.0-CXCR1 ,2,4 and detect the chemotaxis of IL-8 for HEK293 ;establish the experi-mental model of pneumonia induced by the P.aeruginosa,take count of the nucleated cells in the bronchoal-veolar lavage fluid(BALF),analyze myeloperoxidase(MPO) of lung tissue and observe the histopathology changing of it.Results G31P can inhibit the chemotaxis for neutrophils and transfected HEK293 cell line,inhibit the A549 releasing of inflammatory mediators;the proportion of neutrophils declines in G31P treat-ment group,pathology examination appears clear discrepancy.Conclusion G31P can block the chemotaxis of chemotactic factor with ELR+ CXC to neutrophils,block the combination of chemotactic factor with its re-ceptor CXCR2,block the CXCR2 on the surface of alveolar epithelia and vascular endothelial cells.Accordingly,neutrophils recruiting to topoinflammation can be prevented.

EFFECT OF MENOPAUSE ON CHEMOKINE RECEPTOR CXCR2 ON HUMAN MONOCYTE / 解放军医学杂志

To investigate the effect of menopause on chemokine receptor CXCR2 expression on monocyte, 21 postmenopausal and 20 premenopausal women were enrolled in the present study. Fasting venous blood was collected, and plasma estrogen levels were determined with radio immunoassay. Monocytes were separated from peripheral blood with gelatin method. Protein expression of chemokine receptor was assayed with flow cytometry and mRNA concentration was measured with RT PCR. The results showed that the levels of plasma estrogen decreased, whereas protein and mRNA expression of chemokine receptor CXCR2 increased after menopause. The plasma estrogen levels were negatively correlated with chemokine receptor CXCR2 expression in monocytes. These data suggested that the changes in CXCR2 on monocytes might contribute to,at least partially,the increased risk of developing coronary heart disease associated with estrogen secretory changes.

Expression of IL-8 and CXCR2 on Keratinocytes from Psoriatic Lesions / 中华皮肤科杂志

Objective To investigate the expression of IL-8 and CXCR2 on keratinocytes from psoriatic lesions and their roles on clinical and pathologic manifestations. Methods The chemotaxis of psoriatic lesional keratinocytes was detected by micropore loculus test. The concentration of IL-8 was determined in the cultured supernatants of psoriatic keratinocytes by ELISA. The expression of CXCR2 on keratinocytes from affected skin was tested by flow cytometry. Results The chemotaxis for neutrophils by the cultured supernatants of psoriatic lesional keratinocytes was significantly stronger than that by controls. The concentration of IL-8 in the cultured supernatants of psoriatic lesional keratinocytes was also increased. The expression of CXCR2 on psoriatic keratinocytes was significantly increased. Conclusions The psoriatic epidermal hyperproliferation may be correlated with up regulation of IL-8 production and CXCR2 expression on psoriatic keratinocytes. At the same time, the psoriatic inflammation may be partly related to the increase of secretion of IL-8, which has chemotactic capacity, by keratinocytes. IL-8 and CXCR2 may be involved in the pathogenesis of psoriasis.