Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.

ABSTRACT: Alpha-1-antitrypsin (AAT) plays a homeostatic role in attenuating excessive inflammation and augmenting host defense against microbes. We demonstrated previously that AAT binds to the glucocorticoid receptor (GR) resulting in significant anti-inflammatory and antimycobacterial consequences in macrophages. Our current investigation aims to uncover AAT-regulated genes that rely on GR in macrophages. We incubated control THP-1 cells (THP-1^control) and THP-1 cells knocked down for GR (THP-1^GR-KD) with AAT, performed bulk RNA sequencing, and analyzed the findings. In THP-1^control cells, AAT significantly upregulated 408 genes and downregulated 376 genes. Comparing THP-1^control and THP-1^GR-KD cells, 125 (30.6%) of the AAT-upregulated genes a

SUBMITTER: Bai X 

PROVIDER: S-EPMC11252833 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature