Expression and modulatory effects of heme oxygenase in acute inflammation in the rat
- 16 Downloads
Heme oxygenase (HO) is the rate limiting enzyme in the catabolism of heme molecules to the bile pigments which have recently been demonstrated to be strong antioxidants. In this study we analyzed the activity of HO in inflammatory cells isolated from a model of carrageenin induced acute inflammation in the rat. HO activity was significantly higher 24 hours after induction of the inflammation, this increase in activity coincided with the appearance of the highly inducible isoform of HO, Heat Shock Protein 32 kDa (HSP32) as detected by Western Blot analysis. Pre-treatment of animals with Tin protoporphyrin, a HO inhibitor, increased cell exudate at 24 hour in this model by 128% as compared to vehicle control. In comparison pre-treatment with a HO inducer, Ferriprotoporphyrin, decreased inflammatory cell number by 50% and cell exudate by 73% at 24 hours compared to control. These results suggest that HO may represent an endogenous protective mechanism against free radicals in acute inflammation and may be involved in the resolution of acute inflammation. The HSP32 isoform of HO may therefore represent a novel therapeutic target for the modulation of the inflammatory response.
KeywordsHeat Shock Inflammatory Cell Heat Shock Protein Modulative Effect Protective Mechanism
- Maines MD. Heme Oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. Fed Am Soc Exp Biol J 1988;2:2557–68.Google Scholar
- Keyse SM, Tyrell RM. Heme Oxygenase is the major 32-kDA stress protein induced in human skin fibroblasts by UVA radiation, Hydrogen peroxide and sodium arsensite. Proc Natl Acad Sci 1989;86:99–103.Google Scholar
- Stocker R. Induction of haem oxygenase as a defense against oxidative stress. Free Radical Res Comms 1991;9:974–8.Google Scholar
- Tomlinson A, Appleton I, Moore AR, Gilroy DW, Willis D, Mitchell JA, et al. Cyclooxygenase and nitric oxide synthase isoforms in rat carrageenan-induced pleurisy. Br J Pharmacol. In press.Google Scholar