Korean J Anat.
2006 Oct;39(5):393-399.
The Effects of Heme Oxygenase-1 on Collagen Induced Arthritis Model
- Affiliations
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- 1Department of Neurosugery, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
- 2Department of Anatomy, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
- 3Department of Rehabilitation, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
- 4Department of Osthopaedic Surgery, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
- 5Department of Pathology, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea.
- 6Department of Rheumatology, Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk, Korea. ckhlms@wonkwang.ac.kr
Abstract
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Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and
endothelial cells in response to inflammatory stresses. It has been known to show strong immunosuppressive
properties although its mechanisms are not completely understood. This study was designed to determine the effects of
HO-1 modulation on collagen induced arthritis (CIA) model.
CIA model was induced by subcutaneous injection of collagen on tail of DBA/1J mice. For evaluation of HO-1
effects, an inducer of HO-1, cobalt protoporphyrin IX (CoPPIX), or an inhibitor of HO-1, tin protoporphyrin IX
(SnPPIX), were administered every other days into peritoneal cavity from day 1 to day 42 after CIA induction. The
macrocopic clinical findings of CIA were evaluated and histo-pathologic findings and radiographic analysis were
carried out. The expressions of TNF-alpha, IL-6, and VEGF which have important roles in pathogenesis of rheumatoid
arthritis were observed by immuno-histochemical staining.
Collagen on DBA/1J mice induced arthritis at knee joint and ankle joint. Administration of CoPPIX significantly
aggravated the severity of arthritis while SnPPIX protected collagen induced arthritis. SnPPIX strongly suppressed
inflammatory cell infiltration, swelling of synovial membrane, and erosion and destruction of bone on CIA mice.
Furthermore subcutaneous injection of collagen also increased expression of TNF-alpha, IL-6, and VEGF which are
important pro-inflammatory mediators in rheumatoid arthritis. SnPPIX suppressed expression of the pro-inflammatory
mediators on CIA mice. Finally, we suggest that HO-1 mediates the expression of pro-inflammatory mediators and
bone destruction during pathogenesis of CIA, which indicates modulation of HO-1 can be a new therapeutic target of
rheumatoid arthritis.