Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis

Arthritis Rheum. 1999 Sep;42(9):1927-35. doi: 10.1002/1529-0131(199909)42:9<1927::AID-ANR19>3.0.CO;2-X.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arthritis, Rheumatoid / drug therapy
  • Biocompatible Materials
  • Cell Division / drug effects
  • Chemokine CCL2 / biosynthesis
  • Chemotaxis / drug effects*
  • Collagen
  • Drug Combinations
  • Endothelium, Vascular / cytology*
  • Fibroblast Growth Factor 2 / antagonists & inhibitors*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-1 / pharmacology
  • Interleukin-8 / biosynthesis
  • Laminin
  • Mesalamine / pharmacology
  • Mesalamine / therapeutic use*
  • Proteoglycans
  • Solubility
  • Sulfapyridine / pharmacology
  • Sulfapyridine / therapeutic use*
  • Sulfasalazine / pharmacology
  • Sulfasalazine / therapeutic use*


  • Anti-Infective Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biocompatible Materials
  • Chemokine CCL2
  • Drug Combinations
  • Interleukin-1
  • Interleukin-8
  • Laminin
  • Proteoglycans
  • Fibroblast Growth Factor 2
  • matrigel
  • Intercellular Adhesion Molecule-1
  • Sulfasalazine
  • Mesalamine
  • Collagen
  • Sulfapyridine