Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes

Clin Exp Immunol. 1998 Aug;113(2):269-75. doi: 10.1046/j.1365-2249.1998.00621.x.


Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane of multiple joints. This inflammatory microenvironment allows fibroblast-like synoviocytes (FLS) to express or enhance several adhesion or costimulatory molecules. This phenotypic shift, under proinflammatory cytokines, seems to be related to functional consequences for antigen presentation to T cells. The sensory neuropeptide substance P (SP), present at high levels, is able to act on FLS proliferation and enzyme secretion. These data led us to investigate whether SP could also provoke a phenotypic change of FLS. Using flow cytometry and a three-step cellular ELISA method, we determined whether SP has an influence on the expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1), VCAM-1, LFA-3, CD40, B7.1 or B7.2 molecules on RA FLS incubated with interferon-gamma (IFN-gamma) or IL-1beta or tumour necrosis factor-alpha (TNF-alpha) with or without SP. Our results indicate that SP potentiates the effect of proinflammatory cytokines on the expression of VCAM-1 on RA FLS. We verified the presence of specific SP (NK1) receptor mRNA. Using reverse transcription-polymerase chain reaction, we showed that RA FLS of patients express NK1 receptor mRNA. These results suggest that SP increase of cytokine-induced VCAM-1 expression acts via this specific SP receptor. Thus, during chronic inflammation RA FLS are at the interface between the immune and the nervous systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • B7-1 Antigen / analysis
  • CD40 Antigens / analysis
  • CD58 Antigens / analysis
  • Drug Interactions
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class II / analysis
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Tachykinin / analysis
  • Receptors, Tachykinin / genetics
  • Substance P / pharmacology*
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects
  • Synovial Membrane / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*


  • B7-1 Antigen
  • CD40 Antigens
  • CD58 Antigens
  • Histocompatibility Antigens Class II
  • Interleukin-1
  • RNA, Messenger
  • Receptors, Tachykinin
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Substance P
  • Interferon-gamma