Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in osteoarthritic and rheumatoid synovial cells.
OBJECTIVE
Vasoactive intestinal peptide (VIP) has demonstrated beneficial effects in several murine models of immune-mediated inflammation by inhibiting both the inflammatory and the autoimmune components of the disease. We investigate its potential to modulate the release of proinflammatory cytokines and chemokines by human synovial cells from patients with rheumatoid arthritis (RA).


METHODS
Fresh suspensions of synovial tissue cells (STC) or cultured fibroblast-like synoviocytes (FLS) were obtained from patients with RA or osteoarthritis (OA). The effects of VIP on basal or tumour necrosis factor alpha (TNF-alpha)-stimulated production of CCL2 (MCP-1, monocyte chemotactic protein 1), CXCL8 [interleukin (IL)-8], IL-6 and TNF-alpha were studied by specific ELISAs (enzyme-linked immunosorbent assays). The mRNAs for CCL2, CXCL8 and IL-6 in FLS were analysed by real-time reverse transcription-polymerase chain reaction.


RESULTS
VIP at 10 nm down-regulated chemokine production by STC and FLS from RA and OA patients. VIP also down-regulated the expression of mRNAs for CCL2, CXCL8 and IL-6. The effects of VIP were more clearly detected in RA samples and after stimulation with TNF-alpha.


CONCLUSIONS
Our observations confirm that the proposed anti-inflammatory actions of VIP in murine models also apply to human synovial cells ex vivo. Further studies are encouraged to evaluate the use of VIP as a potential therapy for chronic inflammatory joint diseases.
Juarranz
M G
MG
Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, Spain.
Santiago
B
B
Torroba
M
M
Gutierrez-Cañas
I
I
Palao
G
G
Galindo
M
M
Abad
C
C
Martinez
C
C
Leceta
J
J
Pablos
J L
JL
Gomariz
R P
RP
D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide