Chitinase 3 like 1 deficiency ameliorates lipopolysaccharide-induced acute liver injury by inhibition of M2 macrophage polarization

• DOI: 10.1016/j.molimm.2023.02.012
• Publication Date: 2023-03-13T11:48:08Z
• Authors: Minji Kim; Ju Young Chang; Dong won Lee; Yu Ri Kim; Dong Ju Son; Jaesuk Yun; Young Suk Jung; Dong Hun Lee; Sangbae Han; Jin Tae Hong
• Keywords: Lipopolysaccharides; 0301 basic medicine; Mice; 03 medical and health sciences; Liver; Macrophages; Sepsis; Chitinases; Animals; RNA, Messenger; 3. Good health

Chitinase 3-like-1 protein (CHI3L1) is involved in various infectious diseases, especially sepsis. Aberrant CHI3L1 expression potentially plays a critical role in chronic inflammation because a considerable number of macrophages are associated with immune/inflammatory diseases. In this study, we examined the effect of CHI3L1 on hepatic sepsis injury using a lipopolysaccharide (LPS)-induced model. LPS-treated CHI3L1 knockout (KO) mice exhibited a higher survival rate than LPS-treated CHI3L1 wild-type (WT) mice. In addition, hepatic injury-related enzyme levels (aspartate transaminase, alanine transaminase, and lactate dehydrogenase) decreased in CHI3L1 KO mice sera, suggesting attenuated LPS-induced septic liver damage in CHI3L1 KO mice. A greater reduction in the mRNA and protein expressions of M2 polarization markers, such as MRC1, ARG1, IL-10, and IL-4, was observed in LPS-induced CHI3L1 KO mice livers than in LPS-induced WT mice livers. Nonetheless, no change in the mRNA and protein expressions of M1 polarization markers, such as INOS, CD86, TNF-α, and IL6, was noted in LPS-induced CHI3L1 KO mice livers compared with those in LPS-induced WT and KO mice. Similar to the in vivo scenario, liver CHI3L1 depletion in LPS-treated HEP3B cells significantly decreased M2 polarization marker protein expression. However, M1 polarization marker protein expression did not differ significantly. These results suggest that CHI3L1 depletion decreases M2 macrophage polarization, and this effect is potentially associated with the alleviation of liver sepsis in CHI3L1 KO mice.