Manganese Exacerbates ConA-Induced Liver Inflammation via the cGAS-STING Signaling Pathway

AbstractThere is a potential association between the dysregulation of trace elements and impaired liver function. Elevated levels of manganese, an essential metal ion, have been observed in liver-related diseases, and excessive intake of manganese can worsen liver damage. However, the specific mechanisms underlying manganese-induced liver injury are not well understood. The aim of our study was to investigate the effects of excess manganese on autoimmune hepatitis  (AIH) and elucidate its mechanisms. Our findings revealed that manganese exacerbates liver damage under ConA-induced inflammatory conditions. Transcriptomic and experimental data suggested that manganese enhances inflammatory signaling and contributes to the inflammatory microenvironment in the li ver of AIH mice. Further investigations demonstrated that manganese exacerbates liver injury by activating the cGAS-STING signaling pathway and its downstream pro-inflammatory factors such as IFN\(\alpha\), IFN\(\beta\), TNF\(\alpha\), and IL-6 in the liver of AIH mice. These results suggest that manganese overload promotes the progression of AIH by activating cGAS-STING-mediated inflammation, providing a new perspective for the treatment and prognosis of AIH.
Source: Inflammation - Category: Allergy & Immunology Source Type: research