Lipopolysaccharide induces HIF-1α accumulation via MAPK p38-mediated mRNA stabilization and dexamethasone-sensitive protein stabilization.

ABSTRACT: In macrophages, the hypoxia-inducible transcription factor 1α (HIF-1α) can be activated under normoxic conditions by proinflammatory agonists such as lipopolysaccharide (LPS). This noncanonical HIF-1α activation allows macrophages to accommodate rapidly changing demands for energy and biosynthetic precursors in the face of an immune challenge. Alterations in HIF-1α hydroxylation and proteolysis have been implicated in the response, but the involvement of other signaling mechanisms and pathways is unclear. Here, we use genetic and pharmacological approaches to show that LPS-induced HIF-1α accumulation in primary macrophages is dependent on mitogen-activated protein kinase p38 and mediated by the phosphorylation and inactivation of tristetraprolin, an mRNA destabilizing protein that targets

SUBMITTER: Lockwood C 

PROVIDER: S-EPMC12856306 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature