Aldose reductase deficiency inhibits LPS-induced M1 response in macrophages by activating autophagy.

ABSTRACT: Macrophage M1 polarization mediates inflammatory responses and tissue damage. Recently, aldose reductase (AR) has been shown to play a critical role in M1 polarization in macrophages. However, the underlying mechanisms are unknown. Here, we demonstrated, for the first time, that AR deficiency repressed the induction of inducible nitric oxide synthase in lipopolysaccharide (LPS)-stimulated macrophages via activation of autophagy. This suppression was related to a defect in the inhibitor of nuclear factor κB (NF-κB) kinase (IKK) complex in the classical NF-κB pathway. However, the mRNA levels of IKKβ and IKKγ were not reduced in LPS-treated AR knockout (KO) macrophages, indicating that their proteins were downregulated at the post-transcriptional level. We discovered that LPS stimuli induced

SUBMITTER: Cheng P 

PROVIDER: S-EPMC8004403 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature