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Introducción: La artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: Se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR. Resultados: IL-22 e IL-6 fueron similares entre pacientes y controles. Sus niveles disminuyeron luego del tratamiento, principalmente en pacientes respondedores. IL-22 fue menor e IL-6 mayor en LS que en sangre. IL-6 correlacionó positivamente con PCR y anti-CCPhs. Los niveles de VSG, PCR y DAS28 fueron mayores en pacientes con valores dosables de IL-6 que en no dosables. Conclusión: En pacientes con valores basales dosables de IL-22 e IL-6, los niveles de estas citocinas podrían utilizarse como marcador adicional de respuesta al tratamiento.
Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.
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Arthritis, Rheumatoid , Therapeutics , Interleukins , Interleukin-6 , InflammationABSTRACT
AIM:To evaluate the role of heat shock protein 22(HSP22)in atherosclerosis(AS)induced by high-fat diet and in the intervention with atorvastatin(Ator).METHODS: Total 3 groups of 8 ~9-week-old ApoE-/-, HSP22-/-ApoE-/-and HSP22 +ApoE-/-male mice were used,with 18 mice in each group.After 1 week of adaptive feeding, the mice in each group were randomly divided into 2 subgroups: control group, and Ator group, HSP22 knockout group (KO group)and HSP22 knockout with Ator treatment group(KO+Ator group),and HSP22 overexpression group(Tg group)and HSP22 overexpression with Ator treatment group(Tg+Ator group).Atro at 10 mg· kg-1-d-1was administered to the mice in all Ator groups from the 5th week.The mice in the control groups were given saline.All these mice were fed for 13 weeks.Oil red O staining and HE staining of the aortic wall of the mice were used to measure the atherosclerotic le-sion burdens.The protein levels of HSP22,NF-κB, eNOS, ICAM-1 and IL-6 in the aorta and serum were examined by Western blot,immunohistochemistry and ELISA.RESULTS:Aortic Oil red O staining and HE staining showed that the relative area of aorta plaque in Tg group was less than that in KO group(P<0.05).The protein expression of HSP22 in Tg group was significantly higher than that in control group and KO group,and its expression in control group was signifi-cantly higher than that in KO group.The protein expression of eNOS in Tg group and control group was significantly higher than that in KO group.The protein expression of NF-κB and ICAM-1 in control group was significantly decreased as com-pared with KO group,and their expression was significantly higher than that in Tg group.No difference of serum IL-6 level was found among Tg group,KO group and control group.CONCLUSION:HSP22 gene deletion up-regulates the expres-sion of NF-κB and ICAM-1,and down-regulates the expression of eNOS,leading to accelerating AS.HSP22 overexpression decreases the expression of NF-κB and ICAM-1 and increases the expression of eNOS,thus attenuating AS development. HSP22 gene deletion partially limits the role of Ator in the expression of NF-κB,ICAM-1 and eNOS.HSP22 overexpression amplifies the reduced expression of ICAM-1 by the intervention with Ator,and further attenuates AS development.
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Objective To study the role of interleukin-22 (IL-22) in murine asthmatic airway inflammation and airway models, and explore the mechanism of astragaioside (AS) Ⅳin the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice .Thirty-two female specific-free ( SPF) four-week BALB/c mice were randomly divided into 4 groups:control group , asthma group , budesonide treatment group ( BUD group ) and AS-Ⅳgroup.HE staining and AB-PAS were used to measure the inflammation scores and goblet cells hyperplasia , enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF), flow cytometry was performed to analyze the proportion of Th22 cells in spleen single cell suspension , and realtime-PCR was performed to analyze the IL-22 mRNA levels in lung tissue .Results The inflammation scores of asthma group were elevated compared with the control group(P<0.05).An overall reduction of asthmatic airway inflammation was observed in the BUD group and AS-Ⅳgroup by the end of the trial .IL-22 levels in BALF and the proportion of Th22 cells in spleen single cell suspension were significantly increased after treatment in BUD and AS-Ⅳ groups(P<0.01), while the mRNA levels of IL-22 were obviously decreased(P<0.01).Conclusion The increase of IL-22 can induce airway inflammation of asthma . AS-Ⅳcan reduce Th22 cell differentiation and the expression of IL-22, thereby inhibiting the development of airway inflammation of asthma.
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Objective To study the role of interleukin-22 (IL-22) in murine asthmatic airway inflammation and airway models, and explore the mechanism of astragaioside (AS) Ⅳin the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice .Thirty-two female specific-free ( SPF) four-week BALB/c mice were randomly divided into 4 groups:control group , asthma group , budesonide treatment group ( BUD group ) and AS-Ⅳgroup.HE staining and AB-PAS were used to measure the inflammation scores and goblet cells hyperplasia , enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF), flow cytometry was performed to analyze the proportion of Th22 cells in spleen single cell suspension , and realtime-PCR was performed to analyze the IL-22 mRNA levels in lung tissue .Results The inflammation scores of asthma group were elevated compared with the control group(P<0.05).An overall reduction of asthmatic airway inflammation was observed in the BUD group and AS-Ⅳgroup by the end of the trial .IL-22 levels in BALF and the proportion of Th22 cells in spleen single cell suspension were significantly increased after treatment in BUD and AS-Ⅳ groups(P<0.01), while the mRNA levels of IL-22 were obviously decreased(P<0.01).Conclusion The increase of IL-22 can induce airway inflammation of asthma . AS-Ⅳcan reduce Th22 cell differentiation and the expression of IL-22, thereby inhibiting the development of airway inflammation of asthma.
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Objective To study the effect of Interleukin-22 (IL-22) on murine asthmatic airway inflammation and airway remodeling, observe the effect of budesonide on IL-22 of asthmatic mouse model, explore the mechanism of budesonide in the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice.24 female specific-free (SPF) BALB/c mice aged four weeks were randomly divided into 3 groups:control group, asthma group and budesonide treatment group (BUD group).For Histopathological Examination, HE staining was used to measure the inflammation scores, AB-PAS staining was used to measure the hyperplasia of goblet cells and mucin.Enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF).Quantitative Real-time PCR was performed to analyze the effects of budesonide on IL-22 mRNA levels in lung tissue.Results The inflammation scores of asthma group were elevated compared with the control group.An overall change towards less severe asthmatic airway inflammation by the end of the trial was observed in the BUD group.IL-22 levels in BALF were significant decreased after the treatment of budesonide, the mRNA levels of IL-22 were obviously decreased in BUD group, too.A significant positive correlation was observed between the mRNA levels of IL-22 and airway inflammation.Conclusions The increasing IL-22 secretion can lead to the occurrence of airway inflammation of asthma.Budesonide can inhibit the expression of IL-22, thereby Budesonide could inhibit the development of airway inflammation of asthma.
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Aim To investigate whether necroptosis mediates chemical hypoxia-induced HT22 mouse hippocampal cell injury and inflammation.Methods HT22 hippocampal cells were exposed to cobalt chloride (CoCl2) to establish a model of the chemical hypoxia-induced injury and inflammation.The expression level of RIP3 (an index of necroptosis) was determined by Western blot.Cell counter kit-8 (CCK-8) assay was used to test the cell viability.Lactate dehydrogenase (LDH) activity in the culture medium was measured with commercial kits.Mitochondrial membrane potential (MMP) was examined by rhodamine123 staining followed by photofluorography.The intracellular level of reactive oxygen species (ROS) was detected by 2', 7'-dichlorfluorescein-diacetate (DCFH-DA) staining followed by photofluorography.The secretion levels of interleukin-1β (IL-1β) and tumor necrosis factor-a (TNF-α) were measured by ELISA.Results Treatment of HT22 hippocampal cells with 600 μmol·L-1 CoCl2 for 36 h markedly induced cytotoxicity, leading to a decrease in cell viability to (52.0±2.65) % , indicating that chemical hypoxia-induced cellular injury model was successfully set up.Besides, CoCl2 induced considerable injuries and inflammation, evidenced by increases in LDH activity, ROS production, MMP loss, as well as the secretion levels of IL-1β and TNF-α.Co-treatment of the cells with 40~100 μmol·L-1 Nec-1 (a specific inhibitor of necroptosis) and CoCl2 markedly attenuated the decrease in viability induced by CoCl2, reaching the best anti-cytotoxicity inhibitory effect at 80 μmol·L-1.Meanwhile, the co-treatment with 80 μmol·L-1 Nec-1 blocked the above injuries and inflammatory response induced by CoCl2.In addition, treatment of HT22 hippocampal cells for 6~48 h up-regulated the expression of RIP3, and Nec-1 alleviated the up-regulation of RIP3 expression level induced by CoCl2.Conclusion Necroptosis mediates chemical hypoxia-induced HT22 hippocampal cell injury and inflammation.
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Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-gamma (IFN-gamma)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-gamma (10 ng/mL) in a dose dependent manner. Dieckol (5 and 10 muM) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.
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Humans , Chemokine CCL22 , Chemokines , Dendritic Cells , Dermatitis, Atopic , Down-Regulation , Inflammation , Interferon-gamma , Keratinocytes , Killer Cells, Natural , Lymphocytes , Monocytes , Phosphorylation , Skin , TransducersABSTRACT
BACKGROUND: The pathogenesis of psoriasis may involve the interleukin (IL)-23 and Th17-mediated immune responses. Th17 cells secret IL-17 and IL-22, which mediates dermal inflammation and acanthosis. OBJECTIVE: As inhibitor of nuclear factor kappaB kinase-alpha (IKKalpha) has been previously identified as a primary regulator of keratinocyte differentiation and proliferation, we proposed that IL-17 and IL-22 might affect keratinocyte differentiation by changing the expression of IKKalpha. METHODS: We employed HaCaT cells maintained culture medium at a low calcium concentration (0.06 mM) and induced differentiation by switching to the high concentration (2.8 mM) media with IL-17 or IL-22, then compared the IKKalpha expression and the cell cycle. We employed reconstituted human epidermal skin (Neoderm) and mice ears for the in vivo studies. RESULTS: Elevated calcium concentration induced IKKalpha expression and terminal differentiation with cell cycle arrest in HaCaT cell cultures. Moreover, IL-17 and IL-22 treatment also induced IKKalpha in HaCaT cells and reconstituted human epidermis. IKKalpha induction was also noted, following the injection of IL-17 and IL-22 into mice ears. CONCLUSION: Although the induction of IKKalpha was accompanied by keratinocyte differentiation, IL-17 and IL-22 did not affect calcium-mediated differentiation or the cell cycle. Rather, IL-17 and IL-22 appear to contribute to the inflammation occurring via the induction of IKKalpha from keratinocytes or skin layers.
Subject(s)
Animals , Humans , Mice , Calcium , Cell Culture Techniques , Cell Cycle , Cell Cycle Checkpoints , Cell Differentiation , Ear , Epidermis , I-kappa B Kinase , Inflammation , Interleukin-17 , Interleukins , Keratinocytes , Psoriasis , Skin , Th17 CellsABSTRACT
We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-alpha (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.