Upregulation of HO-1 with Haemin Alleviates LPS-Stimulated Pro-inflammatory Responses Through Downregulation of p38 Signalling Pathways in Rat Liver.
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.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
J
J
Tang
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
L
L
Li
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
C-M
CM
Li
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
J
J
Wu
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Y
Y
Sun
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
G-L
GL
Wang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000008:administration & dosage / Q000009:adverse effects; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011524:Protoporphyrins / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006427:Hemin; D051547:Heme Oxygenase-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases