Premium
Upregulation of HO ‐1 with Haemin Alleviates LPS ‐Stimulated Pro‐inflammatory Responses Through Downregulation of p38 Signalling Pathways in Rat Liver
Author(s) -
Tang J.,
Li L.,
Li C.M.,
Wu J.,
Sun Y.,
Wang G.L.
Publication year - 2015
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12352
Subject(s) - downregulation and upregulation , lipopolysaccharide , western blot , zinc protoporphyrin , p38 mitogen activated protein kinases , inflammation , chemistry , secretion , signal transduction , biology , endocrinology , mapk/erk pathway , immunology , biochemistry , enzyme , heme , gene
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, Zn PP , a specific inhibitor of HO ) before LPS stimulation, we evaluated the pathological changes by haematoxylin–eosin staining. The mRNA expression and secretion of IL ‐1 β 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 Zn PP 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.