27-hydroxycholesterol roles in respiratory disease pathogenesis

Abstract

27-Hydroxycholesterol (27-HC) is an oxidative metabolite of cholesterol, enzymatically produced by the mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase (CYP27A1). Endogenous 27-HC maintains cholesterol homeostasis primarily via the selective inhibition of sterol regulatory element-binding protein 2 (SREBP-2). By binding to liver X receptors (LXR) and estrogen receptors (ER), 27-HC exerts diverse biological effects. As the first recognized endogenous selective estrogen receptor modulator (SERM), 27-HC functions as either an ER agonist or antagonist, depending on the tissue microenvironment. In respiratory diseases, 27-HC exacerbates asthma pathogenesis by promoting airway inflammation and remodeling. In lung cancer, 27-HC not only enhances cancer cell proliferation but also stimulates lung adenocarcinoma cell invasion and metastasis. Therefore, targeting 27-HC represents a highly promising therapeutic strategy combatting respiratory diseases.

Keywords: 27-hydroxycholesterol; CYP27A1; ER; LXR; Respiratory diseases.