Upregulation of HO-1 with Haemin Alleviates LPS-Stimulated Pro-inflammatory Responses Through Downregulation of p38 Signalling Pathways in Rat Liver.

Abstract

Haem oxygenase-1 (HO-1) plays an important role in inflammatory disease development and progression. Whether it has an anti-inflammatory role in lipopolysaccharide (LPS)-induced liver injury remains unclear. To investigate the functional role of HO-1 in protecting liver tissue against inflammatory response stimulated by LPS in rat and the mechanism by which it achieves this protective effect, LPS-stimulated inflammatory models were established. In pretreatment of rats with HO-1 activator (haemin) or inhibitor (zinc protoporphyrin-9, ZnPP, a specific inhibitor of HO) before LPS stimulation, we evaluated the pathological changes by haematoxylin-eosin staining. The mRNA expression and secretion of IL-1β and IL-6 in rat liver were analysed using the real-time PCR and ELISA. Real-time PCR and Western blot were also used to evaluate the expression of HO-1, p38 and p-p38 in liver. Liver CO contents were sensitized to the expression of HO-1. Induction of HO-1 by haemin remarkably inhibited the expression of p38, and addition of ZnPP increased this expression. Our results demonstrate that HO-1 is an anti-inflammation factor in LPS-stimulated liver, which regulate the inflammatory response through downregulation of p38 signalling pathways in rat liver.