Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKβ stimulated LOX production.

Abstract	Lysyl oxidase (LOX) is involved in fibrosis by catalyzing collagen cross-linking. Previous work observed that Triptolide (TPL) alleviated radiation-induced pulmonary fibrosis (RIPF), but it is unknown whether the anti-RIPF effect of TPL is related to LOX. In a mouse model of RIPF, we found that LOX persistently increased in RIPF which was significantly lowered by TPL. Excessive LOX aggravated fibrotic lesions in RIPF, while LOX inhibition mitigated RIPF. Irradiation enhanced the transcription and synthesis of LOX by lung fibroblasts through IKKβ/NFκB activation, and siRNA knockdown IKKβ largely abolished LOX production. By interfering radiation induced IKKβ activation, TPL prevented NFκB nuclear translocation and DNA binding, and potently decreased LOX synthesis. Our results demonstrate that the anti-RIPF effect of TPL is associated with reduction of LOX production which mediated by inhibition of IKKβ/NFκB pathway.
Authors	Kaining Guo, Jinran Chen, Zhangjie Chen, Gelian Luo, Shanmin Yang, Mei Zhang, Jinsheng Hong, Lurong Zhang, Chun Chen
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 527 Issue 1 Pg. 283-288 (06 18 2020) ISSN: 1090-2104 [Electronic] United States
PMID	32446381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2020 Elsevier Inc. All rights reserved.
Chemical References	Diterpenes Epoxy Compounds Extracellular Matrix Proteins Phenanthrenes Lox protein, mouse triptolide Protein-Lysine 6-Oxidase I-kappa B Kinase
Topics	Animals Diterpenes (administration & dosage, pharmacology) Dose-Response Relationship, Drug Epoxy Compounds (administration & dosage, pharmacology) Extracellular Matrix Proteins (antagonists & inhibitors, biosynthesis) Female I-kappa B Kinase (antagonists & inhibitors, metabolism) Injections, Intravenous Mice Mice, Inbred C57BL Molecular Structure Phenanthrenes (administration & dosage, pharmacology) Protein-Lysine 6-Oxidase (antagonists & inhibitors, biosynthesis) Pulmonary Fibrosis (drug therapy, metabolism) Radiation Injuries (drug therapy, metabolism) Structure-Activity Relationship

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