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.
Lambert
N
N
Institut National de la Santé et de la Recherche Médicale, Unit 395, Hôpital Purpan, Toulouse, France.
Lescoulié
P L
PL
Yassine-Diab
B
B
Enault
G
G
Mazières
B
B
De Préval
C
C
Cantagrel
A
A
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