Suppression of the CXCL4-JNK pathways contributes to the attenuation of DSS-induced acute colitis in mice

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract with a complex aetiology. Recently, the incidence of the disease has been on the rise and has received additional attention throughout the world. The chemokine CXCL4 was reported to induce directed cellular migration and was involved in the development and progression of inflammatory diseases. Although it has been reported that CXCL4 expression is significantly increased in patients with IBD, the precise role and mechanism of CXCL4 in IBD remain obscure. This study aims to investigate the role of CXCL4 in dextran sulfate sodium (DSS)-induced acute colitis mouse model. The results showed that the serum level of CXCL4 was markedly increased in the acute colitis mice challenged with DSS compared to the control group. Additionally, compared to the control group, the weight loss, survival time, disease activity, colorectal length, and pathological injuries were remarkably increased in the acute colitis mice; moreover, the phosphorylation Jun N-terminal kinase (p-JNK) and the proinflammatory cytokines were significantly up-regulated in the acute colitis mice compared to the control group. In contrast, the above symptoms were notably ameliorated in the DSS-challenged CXCL4 knockout mice. Therefore, the results in the present study indicate that CXCL4 may have a crucial impact on the progression of the inflammatory response during acute colitis through JNKmediated signalling, and it may be a candidate molecule for targeted therapy of IBD.