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Objective To investigate the role of Th22 cells and interlukin 22(IL-22) secreted by Th22 cells in the development of breast cancer. Methods The breast cancer model was established by in situ inoculation of 4T1 breast cancer cells in mice. The experimental group (20 cases) was injected with phosphoric acid buffer (PBS) 0.1 ml containing 4105 4T1 cells into the breast fat pad of mice, while the control group (20 cases) was injected with PBS 0.1 ml into the breast fat pad of mice without cells. Flow cytometry was used to detect Th22 cells in peripheral blood and enzyme linked immunosorbent assay (ELISA) was used to detect the level of IL-22 in serum. The difference of IL-22 levels between Th22 cells and serum was compared between the two groups, and the correlation between Th22 cells and IL-22 was analyzed. Real-time fluorescence quantitative PCR was used to detect the expression of IL-22. The phosphorylation of STAT3 in 4T1 cells treated with IL-22 was detected by Western blot. Results Tumors grew one week after in situ inoculation, and the expression of Th22 cells and IL-22 in serum was significantly increased and positively correlated with that in control group (r＝0.569, P＜0.01 or ＜0.05). The level of IL-22 mRNA in tumor group was significantly increased compared with that in normal group:(22.28 ± 2.52) ng/L vs. (18.92 ± 1.80) ng/L (P＜0.01), and STAT3 was phosphorylated by 4T1 cells after IL-22 treatment. Conclusions Th22 cells and cytokines IL-22 secreted by them can promote the occurrence and development of breast cancer by affecting STAT3 phosphorylation.
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AIM:To investigate the effect of interlukin-22(IL-22)on diabetic nephropathy(DN)and its possible mechanism.METHODS: C57BL/6 mice were randomized to normal control(NC)group,DN group, DN+recombinant IL-22(rIL-22)group and DN+IL-22 antibody(anti-IL-22)group.After successful establishment of diabetes model for 8 weeks,the mice in DN+rIL-22 group and DN+anti-IL-22 group were intraperitoneally injected with rIL-22(200 μg/kg)and anti-IL-22(200 μg/kg),respectively,and the mice in NC group and DN group were intraperito-neally injected with 0.1%bovine serum albumin,twice a week for 4 weeks.After the intervention,blood glucose,kidney function,24 h urine microalbumin(m-Alb)and 24 h urine creatinine(Ucr)were measured.The pathological changes of renal tissues were observed under light microscope.The mRNA expression of Snail1 was detected by qPCR.The protein levels of fibronetin(FN)and E-cadherin were determined by Western blot.RESULTS:After the intervention,the ratio of 24 h m-Alb/Ucr increased significantly in other model groups compared with NC group(P<0.05).The levels of 24 h m-Alb and 24 h Ucr increased significantly in DN +rIL-22 group compared with DN group(P<0.05).However,in DN+anti-IL-22 group,the levels of 24 h m-Alb,24 h Ucr and 24 h m-Alb/Ucr ratio were significantly lower than those in DN group and DN+rIL-22 group(P<0.05).The tubular epithelial cell vacuolar degeneration,protein cast formation and glo-merular mesangial expansion in the renal tissues from diabetic mice were observed under light microscope.The lesions were more severe in DN+rIL-22 group,but attenuated in DN+anti-IL-22 group.The mRNA expression of Snail1 increased sig-nificantly in diabetic mice(P<0.05),but decreased significantly after a 4-week intervention by anti-IL-22(P<0.05). The expression of FN,an extracellular matrix protein,increased significantly in DN +rIL-22 group(P<0.05).The ex-pression of E-cadherin,an epithelial-mesenchymal transition marker,decreased significantly in DN +rIL-22 group as well (P<0.05).CONCLUSION: IL-22 neutralizing antibody may attenuate microalbuminuria and delay the progression of DN via inhibition of Snail1 expression in the renal tubular epithelial cells.
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Objective To investigate the effects of interlukin-22 (IL-22) on diabetic renal fibrosis and its possible mechanisms. Methods C57 BL/ 6 mice were randomized to normal control group ( NC group), diabetic nephropathy control group ( DN group), recombinant interlukin-22 ( rIL-22) group, and interlukin-22 antibody (Anti-IL-22) group. 8 weeks after successful establishment of diabetes model, mice were injected intraperitoneally with 200 ng/ g rIL-22, Anti-IL-22 or equal 0. 1% bovine serum albumin (BSA) twice a week for 4 weeks. After the intervention, blood glucose, kidney function and 24 h urine microalbumin creatinine ratio were measured. Renal pathological changes and collagen deposition were observed under the light microscope, and semiquantitative assessment of renal sclerosis and fibrosis were evaluated at the same time. The mRNA expression of transforming growth factor ( TGF)-β1 was determined by realtime PCR. The protein expressions of α-smooth muscle actin (α-SMA), E-cadherin, and fibronetin (FN) were examined by Western blotting. The protein expressions of collagenⅢ were examined by immunohistochemical analysis. Results After 4 weeks of intervention, the 24 h urine microalbumin creatinine ratio decreased significantly in the Anti-IL-22 group ( P<0. 05). Renal tubular epithelial cells vacuolar degeneration, protein cast formation, and glomerular mesangial expansion were observed under the light microscope. And the lesions were more severe in the rIL-22 group, whereas improved in the Anti-IL-22 group. Meanwhile, the collagen deposition was in accordance with the tubular injury score. Moreover, TGF-β1 gene expression increased significantly in the rIL-22 group (P<0. 01). α-SMA and E-cadherin, epithelial-mesenchymal transition (EMT) markers, increased or decreased significantly in the rIL-22 group respectively (P<0. 05). FN and collagen Ⅲ, extracellular matrix ( ECM ) proteins, increased significantly in the rIL-22 group as well ( P <0. 05). Conclusions IL-22 may induce renal tubular epithelial cells TGF-β1 high expression. As a consequence, this contributes to EMT occurance and ECM accumulation, eventually accelerating the progression of diabetic renal fibrosis.
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Objective To investigate the effects of interlukin-22 (IL-22) on diabetic renal fibrosis and its possible mechanisms. Methods C57 BL/ 6 mice were randomized to normal control group ( NC group), diabetic nephropathy control group ( DN group), recombinant interlukin-22 ( rIL-22) group, and interlukin-22 antibody (Anti-IL-22) group. 8 weeks after successful establishment of diabetes model, mice were injected intraperitoneally with 200 ng/ g rIL-22, Anti-IL-22 or equal 0. 1% bovine serum albumin (BSA) twice a week for 4 weeks. After the intervention, blood glucose, kidney function and 24 h urine microalbumin creatinine ratio were measured. Renal pathological changes and collagen deposition were observed under the light microscope, and semiquantitative assessment of renal sclerosis and fibrosis were evaluated at the same time. The mRNA expression of transforming growth factor ( TGF)-β1 was determined by realtime PCR. The protein expressions of α-smooth muscle actin (α-SMA), E-cadherin, and fibronetin (FN) were examined by Western blotting. The protein expressions of collagenⅢ were examined by immunohistochemical analysis. Results After 4 weeks of intervention, the 24 h urine microalbumin creatinine ratio decreased significantly in the Anti-IL-22 group ( P<0. 05). Renal tubular epithelial cells vacuolar degeneration, protein cast formation, and glomerular mesangial expansion were observed under the light microscope. And the lesions were more severe in the rIL-22 group, whereas improved in the Anti-IL-22 group. Meanwhile, the collagen deposition was in accordance with the tubular injury score. Moreover, TGF-β1 gene expression increased significantly in the rIL-22 group (P<0. 01). α-SMA and E-cadherin, epithelial-mesenchymal transition (EMT) markers, increased or decreased significantly in the rIL-22 group respectively (P<0. 05). FN and collagen Ⅲ, extracellular matrix ( ECM ) proteins, increased significantly in the rIL-22 group as well ( P <0. 05). Conclusions IL-22 may induce renal tubular epithelial cells TGF-β1 high expression. As a consequence, this contributes to EMT occurance and ECM accumulation, eventually accelerating the progression of diabetic renal fibrosis.