Chi3l1 regulates APAP-induced liver injury by promoting macrophage infiltration.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES(2019)
摘要
OBJECTIVE: This study aims to investigate the role of Chi3l1 in Acetaminophen (APAP)-induced liver injury. MATERIALS AND METHODS: In vivo model of liver injury was established in mice administrated with APAP (250 mg/kg) or equivalent phosphate-buffered saline (PBS). Mouse liver tissues were collected at 1 h, 3 h, 6 h, 12 h, and 24 h after treatment, respectively. ALT levels and apoptosis were evaluated. Additionally, we established APAP-induced acute liver injury model in wild-type (WT) mice and Chi3l1-deficient (Chi3l1(-/-)) mice. Pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining. Mononuclear cells (MNCs) were isolated from mouse liver, and the amounts of infiltrating macrophages and neutrophils were then counted by flow cytometry. Serum levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Bone marrow-derived macrophages (BMDMs) were extracted from each mouse. RESULTS: After APAP stimulation, Chi3l1(-/-) mice showed more severe liver injury than that of WT mice, which was manifested as higher ALT levels and more necrotic or apoptotic cells. Compared with WT mice, Chi3l1(-/-) mice expressed higher levels of inflammatory cytokines (MCP-1 and IL-6), macrophage-associated molecules (CD68 and CD86), as well as the amounts of infiltrating macrophages and neutrophils. In addition, higher expressions of inflammatory cytokines were found in BMDMs extracted from WT mice treated with those BMDM lysates derived from Chi3l1(-/-) mice than those of non-treated cells. APAP-treated Chi3l1(-/-) mice exhibited more severe liver injury than that of WT mice. CONCLUSIONS: Our study confirmed that Chi3l1 protects the liver function from APAP-induced injury by inhibiting the secretion of inflammatory factors and macrophage infiltration.
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关键词
APAP,Drug-induced liver injury,Chi3l1
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