Effects of CD11b agonist leukadherin-1 on dextran sulfate sodium-induced acute experimental colitis in mice and the underlying mechanism / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the role of CD11b agonist leukadherin-1 (LA1) in the de-velopment of intestinal inflammation and colitis disease in a mouse model of dextran sulfate sodium ( DSS)-induced colitis. Methods The mouse model of experimental colitis was induced by DSS. Body weight chan-ges and survival status were monitored every day. The length of colons was measured at day 7. Colon tissue sections were stained with hematoxylin and eosin ( HE) and observed under an optical microscope for patho-logical analysis. The percentages of apoptotic cells in colon tissues were observed by TUNEL staining. My-eloperoxidase ( MPO) activity was measured with MPO activity detection kit. IL-1β and TNF-α levels were detected by ELISA. Macrophages and TNF-αin colon tissues were observed using immunofluorescence stai-ning and confocal microscopy. Flow cytometry was performed to detect the changes in TLR4 expression on macrophages after stimulating mice with LA1 for 0, 3, 6 and 12 h. Moreover, TLR4 expression was also measured by Western blot after treating bone marrow-derived macrophages (BMDMs) with LA1 for 0, 3, 6 and 12 h. Unpaired t-test was used for statistical analysis. Results Compared with the DSS group, the LA1+DSS group presented lower mortality rate, greater body weight and longer colon and the differences between the two groups were statistically significant. Moreover, the LA1+DSS group showed lighter pathological dam-ages , decreased percentage of apoptotic cells and suppressed MPO activity as compared with those of the DSS group. The number of macrophages and the relative concentrations of IL-1βand TNF-αin colon tissues were lower in the LA1+DSS group than in the DSS group, and the differences between the two groups were statisti-cally significant. There was no significant difference in the total expression of TLR4 on macrophages before and after LA1 treatment. However, the mean flourscence indensity ( MFI) of TLR4 was weaker on the LA1-treated macrophages than on the untreated macrophages. Conclusions LA1 could alleviate the DSS-induced experimental colitis in mice through suppressing the activation of TLR4 pathway on macrophages. This study provided a new insight and theoretical reference for understanding the pathogenesis of inflammatory bowel diseases.