AIM:To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.METHODS:Seventy-two male Sprague-Dawley rats were randomly divided into thre...AIM:To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.METHODS:Seventy-two male Sprague-Dawley rats were randomly divided into three groups:the sham operation(SO),severe acute pancreatitis(SAP),and melatonin treatment(MT) groups.Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate(4% solution) into the biliopancreatic duct.Melatonin(50 mg/kg) was administered 30 min before pancreatitis was induced,and the severity of pancreatic and pulmonary injuries was evaluated 1,4 and 8 h after induction.Serum samples were collected to measure amylase activities,and lung tissues were removed to measure levels of mRNAs encoding interleukin 22(IL-22) and T helper cell 22(Th22),as well as levels of IL-22.RESULTS:At each time point,levels of mRNAs encoding IL-22 and Th22 were significantly higher(P < 0.001) in the MT group than in the SAP group(0.526 ± 0.143 vs 0.156 ± 0.027,respectively,here and throughout,after 1 h;0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h;0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h,0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h;0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h;0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h,respectively) and significantly lower(P < 0.001) in the SAP group than in the SO group(0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h;0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h;0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h,0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h;0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h;0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h,respectively).The mean pathological scores for pancreatic tissues in the MT group were significantly higher(P < 0.01) than those for samples in the SO group(1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h;2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h;4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h),but were significantly lower(P < 0.01) than those for samples in the SAP group at each time point(1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h;2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h;4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h).The severity of SAP increased significantly(P < 0.01) over time in the SAP group(1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis;and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis).CONCLUSION:Melatonin protects rats against acute pancreatitis-associated lung injury,probably through the upregulation of IL-22 and Th22,which increases the innate immunity of tissue cells and enhances their regeneration.展开更多
AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway invol...AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.展开更多
AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intr...AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.展开更多
BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in ge...BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.展开更多
Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of har...Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.展开更多
文摘AIM:To investigate whether therapeutic treatment with melatonin could protect rats against acute pancreatitis and its associated lung injury.METHODS:Seventy-two male Sprague-Dawley rats were randomly divided into three groups:the sham operation(SO),severe acute pancreatitis(SAP),and melatonin treatment(MT) groups.Acute pancreatitis was induced by infusion of 1 mL/kg of sodium taurocholate(4% solution) into the biliopancreatic duct.Melatonin(50 mg/kg) was administered 30 min before pancreatitis was induced,and the severity of pancreatic and pulmonary injuries was evaluated 1,4 and 8 h after induction.Serum samples were collected to measure amylase activities,and lung tissues were removed to measure levels of mRNAs encoding interleukin 22(IL-22) and T helper cell 22(Th22),as well as levels of IL-22.RESULTS:At each time point,levels of mRNAs encoding IL-22 and Th22 were significantly higher(P < 0.001) in the MT group than in the SAP group(0.526 ± 0.143 vs 0.156 ± 0.027,respectively,here and throughout,after 1 h;0.489 ± 0.150 vs 0.113 ± 0.014 after 4 h;0.524 ± 0.168 vs 0.069 ± 0.013 after 8 h,0.378 ± 0.134 vs 0.122 ± 0.015 after 1 h;0.205 ± 0.041 vs 0.076 ± 0.019 after 4 h;0.302 ± 0.108 vs 0.045 ± 0.013 after 8 h,respectively) and significantly lower(P < 0.001) in the SAP group than in the SO group(0.156 ± 0.027 vs 1.000 ± 0.010 after 1 h;0.113 ± 0.014 vs 1.041 ± 0.235 after 4 h;0.069 ± 0.013 vs 1.110 ± 0.213 after 8 h,0.122 ± 0.015 vs 1.000 ± 0.188 after 1 h;0.076 ± 0.019 vs 0.899 ± 0.125 after 4 h;0.045 ± 0.013 vs 0.991 ± 0.222 after 8 h,respectively).The mean pathological scores for pancreatic tissues in the MT group were significantly higher(P < 0.01) than those for samples in the SO group(1.088 ± 0.187 vs 0.488 ± 0.183 after 1 h;2.450 ± 0.212 vs 0.469 ± 0.242 after 4 h;4.994 ± 0.184 vs 0.513 ± 0.210 after 8 h),but were significantly lower(P < 0.01) than those for samples in the SAP group at each time point(1.088 ± 0.187 vs 1.969 ± 0.290 after 1 h;2.450 ± 0.212 vs 3.344 ± 0.386 after 4 h;4.994 ± 0.184 vs 6.981 ± 0.301 after 8 h).The severity of SAP increased significantly(P < 0.01) over time in the SAP group(1.088 ± 0.187 vs 2.450 ± 0.212 between 1 h and 4 h after inducing pancreatitis;and 2.450 ± 0.212 vs 4.994 ± 0.184 between 4 and 8 h after inducing pancreatitis).CONCLUSION:Melatonin protects rats against acute pancreatitis-associated lung injury,probably through the upregulation of IL-22 and Th22,which increases the innate immunity of tissue cells and enhances their regeneration.
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
基金Supported by the Shandong Provincial Science and TechnologyCommittee of China,No.2014GGH218034
文摘AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.
基金Supported by National Natural Science Foundation of ChinaNo.81370576+2 种基金Application Foundation and Advanced Technology Research Plan of TianjinChinaNo.14JCYBJC24800
文摘AIM: To investigate the therapeutic effects and mechanisms of interleukin(IL)-22 in liver regeneration in mice with concanavalin A(Con A)-induced liver injury following 70% hepatectomy.METHODS: Mice were injected intravenously with Con A at 10 μg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 μg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline.RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3(STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein m RNA expression was significantly elevated after IL-22 treatment.CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy.
基金Supported by Key R&D Plan of Science and Technology Department of Jiangxi Province,No.20171BBG70087
文摘BACKGROUND It is challenging to distinguish intestinal tuberculosis from Crohn’s disease due to dynamic changes in epidemiology and similar clinical characteristics. Recent studies have shown that polymorphisms in genes involved in the interleukin (IL)- 23/IL-17 axis may affect intestinal mucosal immunity by affecting the differentiation of Th17 cells. AIM To investigate the specific single-nucleotide polymorphisms (SNPs) in genes involved in the IL-23/IL-17 axis and possible pathways that affect susceptibility to intestinal tuberculosis and Crohn's disease. METHODS We analysed 133 patients with intestinal tuberculosis, 128 with Crohn’s disease, and 500 normal controls. DNA was extracted from paraffin-embedded specimens or whole blood. Four SNPs in the IL23/Th17 axis (IL22 rs2227473, IL1β rs1143627, TGFβ rs4803455, and IL17 rs8193036) were genotyped with TaqMan assays. The transcriptional activity levels of different genotypes of rs2227473 were detected by dual luciferase reporter gene assay. The expression of IL-22R1 in different intestinal diseases was detected by immunohistochemistry. RESULTS The A allele frequency of rs2227473 (P = 0.030, odds ratio = 0.60, 95% confidence interval: 0.37-0.95) showed an abnormal distribution between intestinal tuberculosis and healthy controls. The presence of the A allele was associated with a higher IL-22 transcriptional activity (P < 0.05). In addition, IL-22R1 was expressed in intestinal lymphoid tissues, especially under conditions of intestinal tuberculosis, and highly expressed in macrophage-derived Langhans giant cells. The results of immunohistochemistry showed that the expression of IL-22R1 in patients with Crohn's disease and intestinal tuberculosis was significantly higher than that in patients with intestinal polyps and colon cancer (P < 0.01). CONCLUSION High IL-22 expression seems to be a protective factor for intestinal tuberculosis. IL-22R1 is expressed in Langhans giant cells, suggesting that the IL-22/IL-22R1 system links adaptive and innate immunity.
基金Supported by National Natural Science Foundation of China,No.81070288 and No.81270452Medical Science and Technology Foundation of Henan Province,No.201001004Science and Technology Leader Overseas Training Foundation of Henan Province,No.201201013
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses.Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract,leading to further inflammation.Interleukin(IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells.Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3signaling cascades.This cytokine induces antimicrobial m olecules and proliferative and antiapoptoic pathways,which help prevent tissue damage and aid in its repair.All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity.In this review,we discuss recent progress in the involvement of IL-22in the pathogenesis of IBD,as well as its therapeutic potential.
