Potential role of heme oxygenase-1 in the progression of rat adjuvant arthritis.
Rat adjuvant arthritis is an experimental model widely used to evaluate etiopathogenetic mechanisms in chronic inflammation. We have examined the participation of heme oxygenase-1 (HO-1) in this experimental arthritis. In this study, an increased nitric oxide (NO) production in the paw preceded the upregulation of HO-1, whereas selective inhibition of inducible NO synthase (iNOS) after the onset of arthritis decreased HO-1 expression, suggesting that the induction of this enzyme may depend on NO produced by iNOS. Therapeutic administration of the HO-1 inhibitor tin protoporphyrin IX was able to control the symptoms of arthritis. This agent significantly decreased leukocyte infiltration, hyperplastic synovitis, erosion of articular cartilage and osteolysis, as well as the production of inflammatory mediators. In this experimental model, HO-1 can be involved in vascular endothelial growth factor production and angiogenesis. These results support a role for HO-1 in mediating the progression of the disease in this model of chronic arthritis.
Devesa
Isabel
I
Department of Pharmacology, University of Valencia, Valencia, Spain.
Ferrándiz
Maria Luisa
ML
Guillén
Isabel
I
Cerdá
José Miguel
JM
Alcaraz
Maria José
MJ
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing); D006614:Hindlimb / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; C090663:N(6)-(1-iminoethyl)lysine; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; C028025:protoporphyrin IX; D010105:Oxygenases; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D008239:Lysine