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

Scand J Immunol. 2015 Nov;82(5):443-51. doi: 10.1111/sji.12352.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Hemin / administration & dosage
  • Hemin / adverse effects
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Protoporphyrins / administration & dosage
  • Protoporphyrins / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Protoporphyrins
  • zinc protoporphyrin
  • Hemin
  • Heme Oxygenase-1
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • p38 Mitogen-Activated Protein Kinases

Associated data

  • RefSeq/NM_0125802
  • RefSeq/NM_0310202
  • RefSeq/NM_031144
  • RefSeq/NM_1739232
  • RefSeq/NM_1740931