Up-regulation of the inflammatory response by ovariectomy in collagen-induced arthritis. effects of tin protoporphyrin IX.
We have studied the influence of ovariectomy on the inflammatory response and bone metabolism on CIA as a model of postmenopausal arthritis as well as the effects of tin protoporphyrin IX (SnPP), a heme oxygenase inhibitor. Ovariectomy in non-arthritic mice produced increased serum PGD2 levels and up-regulated the expression of COX-2, h-PGDS, l-PGDS, and HO-1 in the joints. In CIA, ovariectomy potentiated the inflammatory response with higher levels of serum IL-6 and MMP-3, local PGD2 and MMP-3 as well as trabecular bone erosion. In OVX-CIA, SnPP decreased the serum levels of IL-6, MMP-3, and PGD2; down-regulated TNFα, COX-2, hPGDS, PGD2, PGE2, and MMP-3 in joint tissues; and also decreased focal bone loss in the inflamed joint. Ovariectomy up-regulates inflammatory mediators in non-arthritic and in arthritic animals. In the OVX-CIA model, SnPP exerts anti-inflammatory effects which are not associated with the prevention of systemic bone loss.
Department of Pharmacology, University of Valencia, Av. Vicent Andres Estelles s/n, 46100, Burjasot, Valencia, Spain.
Lidia
L
Ibáñez
Maria José
MJ
Alcaraz
Nuria
N
Maicas
David
D
Guede
José Ramón
JR
Caeiro
Marije I
MI
Koenders
Wim B
WB
van den Berg
Maria Luisa
ML
Ferrándiz
D000818:Animals; D000893:Anti-Inflammatory Agents; D001169:Arthritis, Experimental / Q000473:pathology / Q000601:surgery*; D001842:Bone and Bones / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D007249:Inflammation / Q000209:etiology* / Q000235:genetics; D008665:Metalloporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D010052:Ovariectomy / Q000009:adverse effects*; D017698:Postmenopause; D011524:Protoporphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D008665:Metalloporphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing)