PMID- 10513809
OWN - NLM
STAT- MEDLINE
DCOM- 19991027
LR  - 20220227
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 42
IP  - 9
DP  - 1999 Sep
TI  - Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, 
      inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis.
PG  - 1927-35
AB  - 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.
FAU - Volin, M V
AU  - Volin MV
AD  - Department of Medicine, Northwestern University Medical School, Chicago, Illinois 
      60611, USA.
FAU - Harlow, L A
AU  - Harlow LA
FAU - Woods, J M
AU  - Woods JM
FAU - Campbell, P L
AU  - Campbell PL
FAU - Amin, M A
AU  - Amin MA
FAU - Tokuhira, M
AU  - Tokuhira M
FAU - Koch, A E
AU  - Koch AE
LA  - eng
GR  - AR-30692/AR/NIAMS NIH HHS/United States
GR  - AR-41492/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Anti-Infective Agents)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Biocompatible Materials)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Drug Combinations)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-8)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 119978-18-6 (matrigel)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 3XC8GUZ6CB (Sulfasalazine)
RN  - 4Q81I59GXC (Mesalamine)
RN  - 9007-34-5 (Collagen)
RN  - Y5V2N1KE8U (Sulfapyridine)
SB  - IM
MH  - Anti-Infective Agents/pharmacology
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Arthritis, Rheumatoid/drug therapy
MH  - Biocompatible Materials
MH  - Cell Division/drug effects
MH  - Chemokine CCL2/biosynthesis
MH  - Chemotaxis/*drug effects
MH  - Collagen
MH  - Drug Combinations
MH  - Endothelium, Vascular/*cytology
MH  - Fibroblast Growth Factor 2/*antagonists & inhibitors
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-1/pharmacology
MH  - Interleukin-8/biosynthesis
MH  - Laminin
MH  - Mesalamine/pharmacology/*therapeutic use
MH  - Proteoglycans
MH  - Solubility
MH  - Sulfapyridine/pharmacology/*therapeutic use
MH  - Sulfasalazine/pharmacology/*therapeutic use
EDAT- 1999/10/08 00:00
MHDA- 1999/10/08 00:01
CRDT- 1999/10/08 00:00
PHST- 1999/10/08 00:00 [pubmed]
PHST- 1999/10/08 00:01 [medline]
PHST- 1999/10/08 00:00 [entrez]
AID - 10.1002/1529-0131(199909)42:9<1927::AID-ANR19>3.0.CO;2-X [doi]
PST - ppublish
SO  - Arthritis Rheum. 1999 Sep;42(9):1927-35. doi: 
      10.1002/1529-0131(199909)42:9<1927::AID-ANR19>3.0.CO;2-X.