Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes.
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.
Institut National de la Santé et de la Recherche Médicale, Unit 395, Hôpital Purpan, Toulouse, France.
N
N
Lambert
P L
PL
Lescoulié
B
B
Yassine-Diab
G
G
Enault
B
B
Mazières
C
C
De Préval
A
A
Cantagrel
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D018968:CD58 Antigens / Q000032:analysis; D004347:Drug Interactions; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018039:Receptors, Tachykinin / Q000032:analysis / Q000235:genetics; D013373:Substance P / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D018122:B7-1 Antigen; D019013:CD40 Antigens; D018968:CD58 Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D012333:RNA, Messenger; D018039:Receptors, Tachykinin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; D007371:Interferon-gamma