Beneficial effects of heme oxygenase-1 up-regulation in the development of experimental inflammation induced by zymosan.
Heme oxygenase-1 (HO-1) is part of the integrated response to oxidative stress. This enzyme may exert anti-inflammatory effects in some animal models, although the precise mechanisms are not fully understood. We have examined the role of HO-1 in the inflammatory response induced by zymosan in the mouse air pouch. Zymosan administration induced HO-1 protein expression in leukocytes migrating to exudates, with maximal levels in the late phase of this response (24-48 h). This was accompanied by ferritin induction and bilirubin accumulation, indicating that this enzyme is active in our model. HO-1 expression by zymosan treatment was partly reduced by aminoguanidine, suggesting the participation of endogenous nitric oxide in the mechanisms leading to HO-1 synthesis in the zymosan-injected mouse air pouch. Up-regulation of HO-1 by hemin administration resulted in inhibition of nitric-oxide synthase-2 activity, cellular infiltration into the air pouch exudate, and plasmatic exudation. Leukotriene B4 levels in exudates were significantly decreased in the early phase of this response (4 h), whereas interleukin-1beta and tumor necrosis factor-alpha were inhibited at all time points. Inhibition of HO-1 activity by zinc protoporphyrin IX prevented most of the effects caused by hemin administration. Our results indicate that HO-1 exerts anti-inflammatory effects on the response to zymosan in the mouse air pouch and support a role for this enzyme in the modulation of inflammatory processes.
Vicente
Ana María
AM
Department of Pharmacology, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjasot, Valencia, Spain.
Guillén
María Isabel
MI
Habib
Auïda
A
Alcaraz
María José
MJ
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D015153:Blotting, Western; D002452:Cell Count; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D015777:Eicosanoids / Q000494:pharmacology; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000502:physiology*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000502:physiology*; D015054:Zymosan
D016207:Cytokines; D015777:Eicosanoids; D007375:Interleukin-1; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D006427:Hemin; D015054:Zymosan; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D015232:Dinoprostone; D001663:Bilirubin