Melatonin alleviates circadian rhythm disruption exacerbating DSS-induced colitis by inhibiting the distribution of HMGB1 in intestinal tissues

Abstract

Circadian rhythm disruption (CRD) is regarded as a risk factor for inflammatory bowel disease (IBD), and it was reported to suppress the level of melatonin, which execute anti-inflammatory effects. High mobility group box 1 protein (HMGB1) is a member of the damage-associated molecular pattern (DAMP) family and has been verified as an IBD-associated inflammatory cytokine that mediates the TLR4-NF-κB pathway. However, no exact mechanism has been illustrated among melatonin, disrupted circadian rhythm and inflammatory bowel disease, as well as regarding the effect of melatonin on HMGB1. In the present study, we aimed to explore the role of relationship with HMGB1. CRD aggravated DSS-induced colitis by worsening colonic inflammation and tissue injury, as well as by enhancing HMGB1 translocation, which could be reversed by ethyl pyruvate, an HMGB1 antagonist. Moreover, melatonin treatment attenuated these disorders and the shuttling of HMGB1 in the intestinal epithelial cells (IECs), the effect of which could be partly reversed by the melatonin antagonist luzindole. The protective role of melatonin may be tightly related to the translocation of HMGB1 in IECs. Accordingly, these results suggested that melatonin may be a new therapeutic beneficial option in IBD patients, especially for those with circadian rhythm disruption.