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P018 Macrophage targeting contributes to the inhibitory effects of dihydroartemisinin on DSS-induced colitis

G. Teng*1, W. Ting1, W. Huahong1

1Peking University First Hospital, Gastroenterology, Beijing, China

Background

Macrophages are a major component of the inflammatory milieu, which can be categorised into ‘classically activated’ M1 and ‘alternatively activated’ M2 subtypes based on their polarisation status. Accumulating evidences show that macrophage are key plays in inflammatory bowel diseases (IBD), especially M1 subtype. The present study investigated the role of macrophage targeting in the anti-inflammatory properties of dihydroartemisinin.

Methods

The acute colitis model was induced using DSS as described previously. Macrophages in colon tissue were detected by immunohistochemistry. Typical M1 and M2 markers were determined both in vivo and in vitro. In vitro,macrophage generation were performed using bone marrow cells, and macrophages were detected following dihydroartemisinin treatment.

Results

Dihydroartemisinin significantly resolved the inflammatory response of the colonic epithelium. There was a marked reduction of the colonic infiltration by CD68+ macrophages in mice treated with dihydroartemisinin. Interestingly, both M1 and M2 subtypes were significantly decreased. Concomitantly, CCL2, CSF1, main chemoattractants that support the recruitment and survival of macrophage, were markedly decreased by dihydroartemisinin treatment. And both typical M1 (IL-1β) and M2 (MR, Arg-1) markers were significantly decreased in dihydroartemisinin treated mice. In vitro, consistently, dihydroartemisinin directly reduced the polarisation of M1/M2 macrophage even in the presence of Th1/Th2 cytokines. Moreover, dihydroartemisinin could directly interfere with the generation of macrophage in vitro. These effects of dihydroartemisinin on macrophage were mediated largely via limiting NF-KB signalling.

Conclusion

Dihydroartemisinin inhibited colitis partly by reducing the infiltration and suppressing the function of macrophage.