Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicylic acid, inhibits basic fibroblast growth factor–induced endothelial cell chemotaxis
✍ Scribed by Michael V. Volin; Lisa A. Harlow; James M. Woods; Phillip L. Campbell; M. Asif Amin; Michihide Tokuhira; Alisa E. Koch
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 223 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
Objective:
Rheumatoid arthritis (ra) is characterized by leukocyte recruitment and angiogenesis. we investigated the effects of sulfasalazine (ssz) and its metabolites, sulfapyridine (sp) and 5-aminosalicylic acid (5-asa), on components of angiogenesis, namely, endothelial cell (ec) chemotaxis and proliferation, as well as on ec chemokine and soluble adhesion molecule expression.
Methods:
Ssz, sp, and 5-asa were assayed for their effects on basic fibroblast growth factor (bfgf)-induced human dermal microvascular endothelial cell (hmvec) chemotaxis and proliferation. ec were plated on matrigel to assess the effect of ssz on ec tube formation. enzyme-linked immunosorbent assays were performed to determine changes in hmvec production of interleukin-8 (il-8), monocyte chemoattractant protein-1 (mcp-1), growth-related oncogene alpha (groalpha), epithelial neutrophil-activating peptide 78 (ena-78), soluble e-selectin (se-selectin), and soluble intercellular adhesion molecule 1 (sicam-1) upon treatment with ssz or its metabolites.
Results:
Hmvec incubated with ssz or sp exhibited reduced bfgf-induced chemotaxis (59%, [n = 7] and 22%, [n = 3], respectively) (p<0.05). ssz and sp decreased basal hmvec proliferation, while 5-asa increased proliferation (p<0.05; [n = 5]). ssz decreased bfgf-induced hmvec proliferation (p<0.05 [n = 5]). ssz inhibited phorbol 12-myristate 13-acetate-induced hmvec tube formation (p<0.05; [minimum n = 5]). tumor necrosis factor alpha-stimulated hmvec shedding of sicam-1 was reduced by incubation with either ssz (19%) or 5-asa (23%) (p<0.05; [n = 6]). sp inhibited cytokine-stimulated hmvec expression of il-8 and mcp-1 (p<0.05; [n = 4]). neither ssz nor its metabolites had any effect on hmvec production of se-selectin, groalpha, or ena-78.
Conclusion:
These results demonstrate that ssz and its metabolite sp may affect the pathogenesis of ra by inhibiting ec chemotaxis, proliferation, tube formation, and expression of sicam-1, il-8, and mcp-1.