IL-6 deficiency promotes colitis by recruiting Ly6C < sup > hi < /sup > monocytes into inflamed colon tissues in a CCL2-CCR2-dependent manner

This study aimed to investigate the effect of IL-6 in ulcerative colitis in Il6-/- mice. Results indicated that physiological deficiency of IL-6 promoted the development of colitis. Moreover, IL-6 deficiency significantly increased the mRNA levels of monocytes chemokine Ccl2 and its receptor Ccr2 in colon tissues. Similarly, the percentage of Ly6Chigh monocytes and neutrophils were increased in the colon of Il6-/- mice. Intestinal crypts more strongly increased the migration of Il6-/- macrophages than wild-type ones. Moreover, Il6-/- macrophages promoted the migration of neutrophils. Most importantly, RS102895, an antagonist of CCR2, diminished chemotaxis of macrophages and inhibited colitis in Il6-/- mice. Collectively, these results indicate that Il6-/- macrophages migrate to inflamed colon tissues and recruit neutrophils, thereby promoting the effect of Il6-/- on colitis. This study expands our understanding on the effect of IL-6 deficiency in colitis and the development of gastrointestinal immune adverse effects.PMID:33979652 | DOI:10.1016/j.ejphar.2021.174165

Source: European Journal of Pharmacology - May 12, 2021 Category: Drugs & Pharmacology Authors: Qiuhua Cao Yanting Lin Chongxiu Yue Yue Wang Fei Quan Xinmeng Cui Ran Bi Xinying Tang Yong Yang Chen Wang Xianjing Li Xinghua Gao Source Type: research