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@#[摘 要] 目的：探讨IL-22/IL-22受体A1（IL-22RA1）通路在口腔鳞状细胞癌（OSCC）恶性进展中的作用及其机制。方法：利用GEO数据库和免疫组化法分析IL-22RA1在OSCC组织及配对癌旁组织中的表达水平，采用组织芯片免疫组化法检测并分析IL-22RA1表达水平与OSCC患者临床病理特征的关系，通过EBI ArrayExpress数据库分析IL-22RA1表达水平与患者预后的关系。采用免疫荧光法检测IL-22和IL-22RA1在OSCC组织中表达水平并分析两者间的相关性。用RNA干扰技术敲减OSCC细胞WSU-HN4和CAL27的IL-22RA1表达，用qPCR法验证敲减效率。采用克隆形成实验、Transwell小室法分别检测IL-22对阴性对照（siNC）组和IL-22RA1敲减（siIL-22RA1）组OSCC细胞克隆形成及迁移能力的影响，WB法检测IL-22对OSCC细胞IL-22RA1表达水平及STAT1、STAT3和ERK1/2磷酸化水平的影响。结果：OSCC组织中IL-22RA1 mRNA的表达水平显著高于癌旁组织（P<0.05）。IL-22RA1表达水平与OSCC患者的肿瘤大小（P<0.05）、淋巴结转移（P<0.01）及预后不良（P<0.05）有关联。OSCC组织中的IL-22和IL-22RA1表达水平无明显关联，IL-22对OSCC细胞IL-22RA1表达无影响（均P>0.05）。IL-22可显著增强OSCC细胞的克隆形成和迁移能力（均P<0.01），并可激活OSCC细胞的STAT1、STAT3及ERK1/2信号分子；敲减OSCC细胞的IL-22RA1后，IL-22则无法发挥上述作用。结论：IL-22/IL-22RA1可通过调控细胞增殖和迁移促进OSCC的生长和转移，其下游机制可能是激活ERK1/2-STAT1/3信号通路。
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IL-22 is a member of IL-10 cytokine family. In recent years, increasing evidence has shown that IL-22 is closely related to the immunity in female reproductive tract, and its role in disease development is two-sided. It can not only maintain the balance of microbiota, enhance the resistance to pathogens and reduce the tissue damage caused by infection, but also promote the development and progression of malignant diseases via various signaling pathways. More studies on the biological characteristics and functions of IL-22 are needed for clarifying the pathogenic mechanism and providing new insight into the diagnosis and treatment of female reproductive tract diseases.
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Objective : To investigate the effect of mechanistic target of rapamycin complex 1 (mTORC1) on group 3 innate lymphoid cells (ILC3) function. Methods ¡¤ Intestinal lamina propria leukocytes (LPL) of C57BL/6 wild type mice were stimulated by rapamycin, the specific inhibitor of mTORC1 signaling pathway, in vitro, and then quantity and function of ILC3 were detected by flow cytometry. Next, purified ILC3 from mice intestinal LPL were sorted by flow cytometry. After the activation of ILC3 with IL-23, mRNA expression levels of Rorc (the gene encoding retinoic acid receptor related orphan receptor, i.e. RORγt), Il22 and Rptor (the gene encoding key component protein of mTORC1, i.e. Raptor) were detected by real-time qPCR. For further study, a genetically engineered mouse model specifically knocked out Raptor in ILC3 was constructed. Effects of mTORC1 loss on the quantity and function of ILC3 as well as gut structure were detected by flow cytometry, real-time qPCR and hematoxylin-eosin staining. Results ¡¤ The total ILC3 number had no change, but the secretion of IL-22 by ILC3 reduced after stim-ulation with rapamycin. Il22, Rorc and Rptor mRNA expression levels were upregulated simultaneously in ILC3 after activation with IL-23. In addition, there was no significant difference in the numbers and proportions of total ILC3 and ILC3 subsets as well as gut structure in Rap-tor-deficient mice, but the cytokine IL-22 secretion level of ILC3 significantly decreased in these mice. Conclusion ¡¤ Loss of mTORC1 func-tion inhibits ILC3 from secreting IL-22 but has no effect on the intestinal structure and intestinal ILC3 development, which reveals the positive regulation of mTORC1 signaling on intestinal ILC3 function.
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Objective: To investigate the effect of IL-22 on the expression of Amphiregulin (AREG) in HaCaT and further understand its role in psoriasis vulgaris (PsV). Methods: The mRNA expressions of IL-22, IL-22R1, IL-22BP and AREG were detected by RT-qPCR in PsV lesions (n=26) and healthy control (HC) skin specimens (n=15). RT-qPCR and Western blot were applied to detect the expression of AREG in HaCaT cells stimulated with IL-22 (20 ng/mL) and its soluble receptor IL-22BP (20 ng/mL) for 24 h. Results: The mRNA expressions of IL-22 (P<0.001), IL-22R1 (P<0.001) and AREG (P<0.01) were significantly increased respectively by 36 times, 24 times and 15 times in PsV compared with those in HC. In addition, there were positive correlations between the mRNA levels of AREG and IL-22 (r=0.49, P<0.05). IL-22 could upregulate the mRNA level of AREG by 22 times and protein expression by 6 times in HaCaT cells (P<0.01). IL-22BP could inhibit the effect of IL-22 (P<0.05). Conclusion: IL-22 may regulate positively amphiregulin expression of keratinocytes involved in psoriasis, and IL-22BP may inhibit this role as a blocker in treating psoriasis.
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Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.
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Dermatitis, Atopic , Dermis , Epidermis , Inflammation , Interleukin-13 , Interleukin-4 , Skin , Skin Diseases , T-LymphocytesABSTRACT
Objective To study the significance of serum interleukin(IL)-18,IL-22 and IL-23 levels in rheumatoid arthritis.Methods 40 patients of rheumatoid arthritis w ho received therapy from December 2014 to December 2016 in our hospital were selected,and 40 cases of healthy people in our hospital for the same pe-riod were selected as a control group,the expressions of serum IL-18,IL-22 and IL-23 were compared between the two groups;The relationship between the serum IL-18,IL-22,IL-23 and the severity of rheumatoid arthri-tis,before and after treatment and clinical indicators were analyzed.Results The serum IL-18[(741.82 ± 45.60)pg/mL],IL-22[(62.34 ± 3.72)pg/mL]and IL-23[(141.73 ± 18.31)pg/mL]in rheumatoid arthritis group were higher than that of control group[(231.28 ± 26.71),(37.26 ± 3.91),(48.28 ± 5.70)pg/mL],and the difference has statistical significance(P<0.05);the serum IL-18,IL-22 and IL-23 in highly active group rheumatoid arthritis patients were significantly higher than that of moderate active group and stable/mild ac-tive group,serum IL-18,IL-22 and IL-23 in the moderate active group were significantly higher than that of stable/mild active group,and the difference has statistical significance(P<0.05);after treatment,the serum levels of IL-18,IL-22 and IL-23 in patients with rheumatoid arthritis were significantly lower than those before treatment,and the difference has statistical significance(P< 0.05);the results of correlation analysis show that there was a positive correlation between the serum IL-18 and joint tenderness index,joint swelling index, C reactive protein and bone destruction score(P<0.05),and there was a positive correlation between the ser-um IL-22,IL-23 and VAS score,the time of morning stiffness,joint pain index,swelling index,platelet count,C reaction protein and done destruction score(P<0.05).Conclusion The serum IL-18,IL-22,and IL-23 are closely related to the severity of rheumatoid arthritis,which can increase with the aggravation of disease,and it also helps to assess the effectiveness of disease treatment,application value is high.
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Objective@#To explore the levels of IL-22 in thymus damaged by γ-ray total body irradiation (TBI), and to study the role of IL-22 in T cell reconstitution after thymic injury induced by TBI.@*Methods@#To induce thymic injury, mice were treated by sub-lethal TBI. Levels of intra-thymic and circulatory IL-22 were detected by using ELISA assay. Untreated mice were used as control. After receiving sub-lethal TBI, mice were intraperitoneally injected with PBS or recombinant mouse IL-22, which were marked as TBI+PBS or TBI+IL-22, respectively. Mice were monitored for counts of total thymic cells and circulatory white blood cells. Flow cytometry was applied to analyze percentages of thymic epithelial cells (TEC), thymocyte subsets and circulatory T cells. Real-time PCR assay was applied to analyze the mRNA expression levels of Foxn1, Ccl25, Aire and Dll4 in thymus.@*Results@#①Sub-lethal TBI treated mice expressed higher levels of intra-thymic and circulatory IL-22, compared with untreated ones (all P<0.05). ②After injection of recombinant IL-22, TBI+IL-22 mice had higher levels of intra-thymic IL-22 than TBI+PBS mice (all P<0.05). ③On day 14 after irradiation, real-time PCR assay showed that TBI+IL-22 mice had higher mRNA levels of Foxn1, Ccl25, Aire and Dll4 in thymus compared with TBI+PBS ones. Meanwhile, the TBI+IL-22 mice had higher counts of total thymic cells[(5.93±3.19)×106/ml vs (1.42±0.46)×106/ml, t=3.128, P=0.033] and circulatory white blood cells[(3.08±0.94)×106/ml vs (1.43±0.30)×106/ml, t=3.730, P=0.015] than those of TBI+PBS mice. Flow cytometry analysis indicated that TBI+IL-22 mice had higher counts of TEC and thymocytes than TBI+PBS mice on day 14 after irradiation (all P<0.05). On days 7 and 14 after irradiation, TBI+IL-22 mice had higher counts of circulatory white blood cells and T cells than TBI+PBS mice (all P<0.05).@*Conclusion@#Sub-lethal TBI induces upregulation of intra-thymic IL-22, and injecting of recombinant IL-22 increases level of IL-22 in thymus. Injecting of recombinant IL-22 improves recovery of TEC and increases numbers of thymocyte subsets and circulatory T cell after thymic injury.
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Objective:To observe the expressions of Th22 cells and IL-22 in peripheral blood of patients with Lupus nephritis (LN) and explore its significance.Methods: Patients of systemic lupus erythematosus (SLE) with no renal involvement (n=38),lupus nephritis (n=32) and healthy controls (n=10) were studied.Flow cytometry was utilized to quantify the percentage of Th22 cells in peripheral blood.Enzyme-linked immunosorbent assay was used to detect the levels of serum IL-22.The Th22 cells and The serum level of IL-22 among three groups were compared,and the correlation between Th22,IL-22 and SLE disease activity index score (SLEDAI) was analyzed.Results: Th22 cells in SLE group and LN group were significantly higher than those in healthy control group (P0.05).The proportion of Th22 cells and the level of IL-22 in LN group were positively correlated with the disease activity score SLEDAI.Conclusion: Th22 cells and IL-22 may play an important role in the pathogenesis of SLE and LN.
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Objective To explore the effects of Sishen Pill and Gegen Qinlian Tablet on cytokines of acute and chronic colitis induced by dextran sulfate sodium (DSS) in mice. Methods Mice freely drank 4%DSS dissolved in drinking water for continuous 5 days to establish acute colitis model. Mice circularly drank 3% DSS for 4 times for the establishment of chronic colitis model. In the acute or chronic colitis experiment, mice were randomly divided into control group, acute and chronic model groups, Sishen Pill group, and Gegen Qinlian Tablet group. Acute model group was administrated one day after DSS drinking for 8 days. Chronic model group was administrated after the second time of circular drinking for 16 days. ELISA was used to detect the contents of IFN-γ, IL-17 and IL-22 in cultural supernatant of mouse colon. Results Contents of IFN-γ, IL-17A and IL-22 in cultural supernatant increased significantly in acute models (P<0.01). Gegen Qinlian Tablet can significantly decrease the contents of IFN-γ and IL-17A of acute models (P<0.05). Sishen Pill can significantly decrease the content of IL-17A (P<0.05). IFN-γand IL-17A in cultural supernatant in chronic model mice significantly increased compared with control group (P<0.01). Sishen Pill and Gegen Qinlian Tablet inhibited the contents of IFN-γ and IL-17A. Compared with control group, Sishen Pill significantly increased the content of IL-22 (P<0.05). Conclusion Sishen Pill and Gegen Qinlian Tablet can treat colitis by decreasing the contents of IFN-γ and IL-17A in acute colitis model mice;Sishen Pill can treat chronic colitis by promoting IL-22 to increase.
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Objective to measure the percentage of th22 cells and evaluate the levels of plasma interlukin-22(IL-22)in human peripheral blood, so as to determine their clinical significance in primary Sj?gren′s syndrome(pSS). Methods Patients with pSS were divided into three subgroups based on severity of labial gland involvement:mild,moderate and severe. Healthy people served as controls. the percentage of th22 cells and the lev-els of IL-22 in human peripheral blood from pSS patients and healthy controls were measured and compared. Results Compared to healthy con-trols,pSS patients had significantly higher percentage of th22 cells and higher plasma IL-22 levels(P < 0.05). Among pSS patients,the more seri-ous illness they had,the higher percentage of th22 cell and levels of IL-22 were observed. Severe patients had higher percentage of th22 cells and IL-22 levels than moderate patients(P < 0.05),and moderate patients had higher percentage of th22 cells and IL-22 levels than mild patients(P <0.05). Conclusion Increased peripheral IL-22-secreting th22 cells are detected in primary Sj?gren′s syndrome,which have a close association with disease severity. these data suggest that th22 and its released cytokine IL-22 may be considered as potential valuable biomarkers for severity of pSS,which may provide a novel therapeutic target for treatment.
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Objective To study serum IL-22 levels in patients with pulmonary tuberculosis and diabetes mellitus (PPTDM) and to analysis their clinical significance.Methods ELISA was used to detect serum IL-22 levels in 30 cases PPTDM pa-tients,30 cases pulmonary tuberculosis (PTB)patients,30 cases diabetes mellitus (DM)patients and 30 cases healthy vol-unteers (HV).Results Serum IL-22 levels of PPTDM patients (54.4±4.81 pg/ml)were significantly lower than those in diabetes mellitus (DM)patients (72.36±5.12 pg/ml)and healthy volunteers (HV)(68.32±3.08 pg/ml)(t=2.557,P =0.013;t=2.437,P =0.018),respectively.There was no significantly different of serum IL-22 levels between PPTDM and PTB patients (t=1.190,P =0.239).Serum IL-22 levels of diabetes mellitus coincident with pulmonary tuberculosis (DM-PTB)patients (64.62±8.59 pg/ml)were significantly higher than those in pulmonary tuberculosis coincident with diabetes mellitus (PTB-DM)patients (44.21±2.68 pg/ml)(t=2.267,P =0.031).Conclusion IL-22 may play an important role in PPTDM development.
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Objective To investigate the expression of T helper type 17 cells (Th17) and cell‐related cytokines ,including interleukin (IL)‐21 ,IL‐22 ,IL‐23 in the peripheral blood of different clinical stages of patients with acute hepatitis B (AHB) .Methods Ten cases of AHB patients were enrolled .The frequency of Th17 cells in the three clinical stages (i .e .acute phase ,convalescent phase and resolved phase) were detected by flow cytometry . IL‐21 , IL‐22 and IL‐23 were measured by enzyme‐linked immunosorbent assay (ELISA) .Control group was composed of ten healthy subjects .The comparison between the two groups was done by t test and the differences among multiple groups were compared by one way ANOVA .Pearson correlation analysis was used for correlation analysis .Results The frequency of Th17 in healthy controls was (0 .68 ± 0 .29)% ,while those in acute phase ,convalescent phase and resolved phase of AHB patients were (18 .22 ± 4 .13)% , (3 .14 ± 1 .90 )% and (3 .31 ± 0 .95 )% , The differences between the two groups were significant (t= 13 .405 ,4 .047 and 8 .342 , respectively ;all P< 0 .01) .The levels of IL‐21 ,IL‐22 and IL‐23 in healthy controls were (42 .00 ± 6 .95) ,(315 .89 ± 96 .16) and (11 .95 ± 6 .95) ng/L ,respectively .Those in acute phase of AHB patients were (575 .39 ± 47 .01) ,(648 .44 ± 47 .12) and (38 .29 ± 4 .68) ng/L ,respectively ,those in convalescent phase were (366 .50 ± 33 .74) ,(405 .04 ± 47 .12) and (25 .10 ± 4 .69) ng/L ,respectively ,while those in resolved phase of AHB patients were (46 .62 ± 8 .28) ,(365 .94 ± 45 .62) and (15 .29 ± 4 .69) ng/L , respectively .Compared with healthy controls ,t values of the levels of IL‐21 in three different phases of AHB patients were 35 .497 ,29 .792 and 1 .354 with P value of <0 .01 ,<0 .01 and 0 .193 ,respectively ;those of IL‐22 were 9 .820 ,2 .632 and 1 .487 with P value of < 0 .01 ,0 .021 and 0 .161 ,respectively ;those of IL‐23 were 9 .944 ,4 .961 and 1 .260 with P values of <0 .01 ,<0 .01 and 0 .226 ,respectively . After comparison of IL‐21 ,IL‐22 and IL‐23 among three different phase of AHB ,F values were 622 .784 , 107 .772 and 60 .743 with all P values less than 0 .01 ,respectively .The levels of IL‐21 ,IL‐22 and IL‐23 were all positively correlated with the serum ALT level in acute phase (r= 0 .655 ,0 .666 and 0 .673 , respectively ;all P<0 .05) .Correlation analysis demonstrated that the frequency of Th17 was positively correlated with the levels of IL‐21 , IL‐22 and IL‐23 in acute phase ( r= 0 .879 ,0 .866 and 0 .879 , respectively ;all P<0 .01) .The frequency of Th17 was positively correlated with the level of IL‐21 in the resolved phase . No correlations between the remaining groups were confirmed . Conclusion The expressions of Th17 and cell‐related cytokines ,including IL‐21 ,IL‐22 and IL‐23 decline with the recovery of A HB .
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This study was aimed to investigate the effect of baicalin on the proportion of Th22 cells and the concentration of IL-22 bothin vivo andin vitro, in order to explore the immune mechanism of baicalin on inflammatory bowel disease mice model. The 3.5% dextran sodium sulfate (DSS) was used on C57BL/6 mice for the establishment of colitis mice model. Mice were randomly divided into the blank control group, model group, and baicalin group. Flow cytometry and ELISA were used in the detection of the proportion of Th22 cells and concentration of IL-22 in peripheral blood serum, respectively. The spleen lymphocytes of mice were isolated and cultured by baicalin medium (0, 10, 20, 40μM) for 48 h. Flow cytometry was used in the detection of the proportion of Th22 cells. The results showed that baicalin reduced the proportion of Th22 cells and the expression of IL-22 bothin vivo andin vitro experiments. It was concluded that baicalin can inhibit Th22 cell differentiation and expression of IL-22in vitro and DSS-induced colitis mice. It indicated that baicalin had a good treatment potential in Th22 cell-mediated inflammatory diseases.
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Objective To investigate the dynamic expressions of interleukin-22(IL-22),Interleukin-22 receptor 1(IL-22R1),and hepatic stellate cells(HSC)senescence in mice with Schistosoma japonicum infection. Methods A murine model of S. japonicum infection was established and the serum samples and liver tissues were collected 4,6,8,12 weeks post-infection. The serum samples were detected for the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST). The pathological changes and proliferation of hepatic collagen fibers in the liver tissue were observed after HE staining and Masson staining. The HSC senescence in fibrotic livers was determined by the detection of senescence-associatedβ-galactosidase(SA-β-Gal). Sandwich ELISA was used to measure the expressions of IL-22,and Real-time PCR was used to test the mRNA levels of IL-22 and IL-22R1. The control group without S. japonicum infection was set up. Results The serum levels of ALT and AST signifi-cantly increased 8 weeks and 12 weeks after the infection(vs. 0 week,all P<0.05). The level of IL-22 increased 4 weeks and 6 weeks after the infection(vs. 0 week,both P<0.05),but reduced 8 weeks post-infection,and was even lower 12 weeks post-in-fection(vs. 4 weeks and 6 weeks,both P<0.01). Being consistent with the dynamic expression of IL-22 protein,the mRNA ex-pression of IL-22 began to increase 4 weeks and reached the peak 6 weeks after the infection(vs. 0 week,both P<0.05),and continuously declined 8 weeks and 12 weeks post-infections(vs. 6 weeks,both P<0.05). The increase of the expression of IL-22R1 mRNA was correlated with the progression of fibrosis,and the peak was in 12 weeks post-infections(vs. 0 week and 6 weeks,both P<0.05). The number of senescence-associated beta-galactosidase-positive HSCs was reduced with the decreasing expression of IL-22 in the advanced liver fibrosis. Conclusion IL-22 and IL-22R1 are involved in the pathogenesis of schistoso-miasis liver fibrosis. As an inflammation factor,IL-22 significantly increases in the early stage of fibrosis. The expression of IL-22 decreases in the late stage of fibrosis,which may contribute to HSC senescence and restrict liver fibrosis.
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Objective To investigate the changes of Th17 and Th22 cells in patients with Helicobacter pylori(HP)infection . Methods 66 cases of HP infection (HP infection group) and 30 cases of healthy people (control group) were selected .The levels of Th17 and Th22 cells in peripheral blood were measured by flow cytometry and the level of IL-17 and IL-22 in serum were meas-ured by ELISA .Results Comparing with the control group ,the levels of Th17 ,Th22 ,IL-17 and IL-22 were significantly increased in HP infection group(P<0 .05) .The correlation analysis showed that the levels of Th17 ,Th22 ,IL-17 and IL-22 were significantly positive correlated with DPM(P<0 .01) .Conclusion Th17 and Th22 cells were actived in patients with HP infection ,which caused the high expression of immune effector molecules ,and promoted the progress of immune damage .
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Objective To investigate whether a novel long-acting tumor necrotic factor (TNF) antagonist (soluble TNF receptor:IgG Fc [sTNFR:IgG-Fc]) can protect hepatocyte damage against liver failure caused by drugs in immunity-induced cirrhotic rats.Methods Wistar rats were repeatedly sensitized by human serum albumin (HSA) emulsified in complete freud adjuvant.The blood was collected at day 10 after the final sensitization.If anti-albumin antibody was positive,the rats were intravenously injected with HSA twice a week.After six weeks,liver cirrhosis was induced by immunity.All the model rats were divided into three groups with 15 each.Liver failure was induced with D-galactosamine/ lipopolysaccharide (LPS) intraperitoneal injection in the rats with liver cirrhosis in model group.The rats in pretreatment group were intraperitoneally injected with long-acting soluble TNF receptor p55 18 h before D-galactosamine/LPS injection.The control group were injected with 0.9％ sodium chloride.General condition,survival rate,liver function and pathological changes were all examined.Serum levels of interleukin (IL)-6,IL-22 and intrahepatic level of IL-6 were detected by enzyme linked immunosorbent assay (ELISA).The activity of Caspase 3 in hepatocyte lysis solution was measured by spectrophotography.Real-time polymerase chain reaction (PCR) was used to detect mRNA expressions of proliferating cell nuclear antigen (PCNA),bcl-2,bax and IL-22 receptor.Data were analyzed by variance analysis among groups.Results Rats in model group were dispirited with poor response after 12 hours and only 3 survived,compared with soluble TNF receptor p55 pre-treated group rats,in which all survived (P=0.029 8) with flexible response.Serum alanine aminotransferase levels in these two groups were (6 533± 360) and (105 ± 7) U/L,respectively.Hepatic regenerative nodule developed massive or submassive necrosis with septal fibrosis in model group,whereas soluble TNF receptor p55 alleviated the inflammatory and necrosis reaction of hepatic tissue.Serum IL-6 levels in model group and pretreatment group were (842.0±12.9) and (91.9±1.6) pg/mL,respectively (F=380.30,P＜0.01).Intrahepatic levels of IL-6 in these two groups were (26.2±1.2) and (11.1±0.8) pg/mL,respectively (F=176.90,P＜0.01),and serum IL-22 levels were (167.0±27.8) and (988.0±109.6) pg/mL,respectively (F=37.91,P＜0.01).Hepatic Caspase-3 activity was reduced by almost 60％ by soluble TNF receptor p55 pretreatment (F=303.70,P＜0.01) and bax expression reduced by 22％ (F=108.80,P＜0.01),while bcl-2 and PCNA expressions were up-regulated by 3.6-folds and 23.0-folds,respectively (F=115.60,P＜0.01; F=594.20,P＜0.01).Conclusions Long acting soluble TNF receptor p55 could improve survival rate,liver function and reduce inflammatory reaction of rats with liver failure induced by drugs on the basis of liver cirrhosis caused by immunity,which indicates that this drug may process a potential therapeutic value.
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Th22,a new subset of helper T cells,which is char-acterized by the secretion of interleukin-22(IL-22),could infil-trate to the epidermis in individuals with inflammatory skin disor-ders.This article introduces the action of Th22 and IL-22 in in-flammatory skin diseases,including psoriasis,atopic dermatitis, systemic lupus erythematosus,systemic sclerosis,aiming at re-vealing the role of Th22 and IL-22 in these diseases,which would not only provide some novel targets of drugs for inflamma-tory skin diseases,but also promote the researches on the pre-vention and treatment of these diseases.
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OBJECTIVE@#To investigate the protective effect of IL-22 and IL-12 on cutaneous leishmaniasisin BALB/c mice.@*METHODS@#The protective effect of IL-22 and IL-12 on cutaneous leishmanias in BALB/c mice was evaluated by measurement of IL-4, INF-γ, total IgG, IgG1 and IgG2a after challenge with Leishamania major. Clinical evaluations were performed by measurement of lesion diameter, and survival rate of the mice.@*RESULTS@#In week 27 post infection, the mortality rates for control groups were 100%. While the survival rates for the IL-12, IL-12 + IL-22, and IL-22(5 ng/g) groups were 100%. The size of lesions decreased in the presence IL-22 (5 ng/g) of mice weight, which was statistically significant in comparison with other groups (P<0.05). Mean of total IgG, IgG1 and IgG2a for IL-22 (5 ng/g) group was more than other groups. In IL-22 group (5 ng/g), INF-γ production was significantly higher than other groups and IL-4 was significantly lower than other groups.@*CONCLUSIONS@#The results obtained indicate the effectiveness of IL-22 and its effect on IL-12 in protection of cutaneous leishmaniasis.
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Objective: To investigate the protective effect of IL-22 and IL-12 on cutaneous leishmaniasisin BALB/c mice. Methods: The protective effect of IL-22 and IL-12 on cutaneous leishmanias in BALB/c mice was evaluated by measurement of IL-4, INF-γ, total IgG, IgG1 and IgG2a after challenge with Leishamania major. Clinical evaluations were performed by measurement of lesion diameter, and survival rate of the mice. Results: In week 27 post infection, the mortality rates for control groups were 100%. While the survival rates for the IL-12, IL-12 + IL-22, and IL-22(5 ng/g) groups were 100%. The size of lesions decreased in the presence IL-22 (5 ng/g) of mice weight, which was statistically significant in comparison with other groups (. P<0.05). Mean of total IgG, IgG1 and IgG2a for IL-22 (5 ng/g) group was more than other groups. In IL-22 group (5 ng/g), INF-γ production was significantly higher than other groups and IL-4 was significantly lower than other groups. Conclusions: The results obtained indicate the effectiveness of IL-22 and its effect on IL-12 in protection of cutaneous leishmaniasis.
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Objective To investigate the characteristics of IL-22 in Helicobacter pylori (H.pylori)infection.Methods Thirty H.pyloripositive and fifteen H.pylori negative gastric biopsy specimens were enrolled,IL-22 mRNA expression was detected by real-time PCR and the protein level of IL-22 was determined by ELISA in gastric tissue.The H.pyloriand cell coculture system was established and IL-22 expression was measured by real-time PCR to investigate the main source of IL-22 in gastric tissue.The IL-22-producing T cell was examined by FCM in the gastric mucosa tissue.Results Gastric mucosal IL-22 mRNA and protein levels were significantly higher in H.pylori-positive patients than uninfected patients (P＜0.05).A H.pyloriand cell coculture system was established successfully and gastric epithelial cell and T cell were the main source of IL-22 in gastric tissue.IL-22 was produced by CD4+ and CD8+ T cells and these T cells were increased in H.pylori-infected gastric mucosa (P＜0.05).Conclusion IL-22 took part in H.pyloriinfection induced immune response and increased IL-22-producing T cells was the important feature of H.pyloriinfection.