TPL-2 regulates inflammation in ulcerative colitis through activating JNK/ERK pathway

Abstract

Abstract Purpose: To investigate the roles of Tumor progression locus 2 (TPL2)on regulating the inflammation in patients with ulcerative colitis (UC). Methods: Colonic biopsies, serum samples and demographic features were collected from healthy volunteers and UC patients. Subsequently, HE staining were taken to evaluate the degree of intestinal mucosal damage and inflammation from 10 patients. The expression levels of TPL2, iNOS and COX2 was examined by western blot and immunohistochemistry. Quantitative Real Time PCR was performed to detect the production of IL-6, IL-10 and IL-18. Additionally, the expression of TPL2 was knocked down by siRNA to further explore its role in inflammation regulation in vitro. The expression of p-JNK, JNK, p-ERK and ERK was also detected by western blot to demonstrate the mechanisms of TPL2. Results: There was no significant difference in gender, and age of disease between the controls and UC groups. Histological damage scores and inflammation scores with statistically difference demonstrated a gradient increase in patients with mild and severe UC compared to control group. Furthermore, Western blot assay and qRT-PCR showed no substantial difference in TPL2 expression between patients with mild UC and controls, while it was significantly upregulated in severe UC patients. Meanwhile, the expression of iNOS and COX2 was not remarkably different from the normal controls, whereas it was significantly upregulated in severe UC patients. We further revealed that the JNK/ERK pathway was activated by up regulation of TPL-2. Conclusions: TPL2 significantly upregulates the inflammation in UC patients, which has regulatory effects on iNOS and COX2 through the ERK and JNK pathways. These results suggest that TPL2 is a potential therapeutic target for the treatment of UC.