Effects Of A Selective JNK Inhibitor On Mice With DSS-induced Ulcerative Colitis

Aims:To develop mice with ulcerative colitis(UC) induced by dextran sulfate sodium (DSS). And then to evaluate the influence of selective c-Jun N-terminal kinase(JNK) inhibitor SP600125 on the expressions of p-JNK,tumor necrosis factor(TNF)-a in the colonic mucosa and serum levels of interleukin(IL)-6.Methods:Forty male C57BL/6 mice were randomly assigned to five groups(A-E): group A(Control),group B(DSS induced colitis),group C (low dosage of SP600125),group D (large dosage of SP600125),groupE(DMSO control).Animals in Group B to group E were only given 3% DSS solution as drinking water for 7 days to induce acute intestinal inflammation;those in Group A had free access to distilled water.Mice in Group C and group D also received intraperitoneal SP600125 injection(10 mg/kg or 20 mg/kg, 2 h before the induction of colitis with DSS). Mice in Group E only received DMSO.The animals were sacrificed on the 7th day , and the disease activity index(DAI)and histological index (HI)were examined, the changes of p-JNK,TNF-αwas measured by immunohistochemistry,the level of IL-6 was measured by ELISA.Results:DAI(8.000±1.414) and HI (5.875±0.991) in group B were significantly higher than those in the group A (DAI 0.250±0.463, HI 0.500±0.926, P <0.01 respectively), The DAIs in group C (5.875±1.642) and group B (8.000±1.414) was no significantly different(P>0.05), DAI in group D(4.375±1.506) was significantly lower than that in group B(8.000±1.414, P <0.01).HIs in group C (3.875±1.458) and group D (2.500±0.756) were significantly lower than those in the group B (5.875±0.991, P<0.01, respectively).The levels of p-JNK(99.005±0.753), TNF-a(103.394±1.090), and IL-6 (183.338±25.869) in group B were significantly higher than those in the group A (p-JNK 116.413±0.456, TNF-a 120.244±0.666, IL-6 75.912±20.270, P<0.01, respectively), Those in group C (p-JNK 105.939±0.929, TNF-a 110.206±1.051, IL-6 140.368±32.066)and group D(p-JNK 114.516±1.060, TNF-a 117.868±0.997, IL-6 108.606±20.344) were significantly lower than in the group B(P <0.01, respectively).Conclusion:The JNK was over expressed in mice colonic mucosa with ulcerative colitis induced by DSS.The JNK inhibitor SP600125 can down-regulate the expression of TNF-αin colonic mucosa and IL-6 in the serum, and degrade the DAI and HI.