Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis.
OBJECTIVE
To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA.


METHODS
The effects of SOM on proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) and collagenase production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT-PCR. Local production of SOM was estimated by RT-PCR and immunohistochemical staining.


RESULTS
Physiologic concentrations (approximately 10(-10)M) of SOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast-like synovial cells, and the expression of SOMR-2 was up-regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA.


CONCLUSIONS
SOM inhibited aberrant synovial cell function in patients with RA, suggesting possible clinical applications of this neuropeptide.
Takeba
Y
Y
St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Suzuki
N
N
Takeno
M
M
Asai
T
T
Tsuboi
S
S
Hoshino
T
T
Sakane
T
T
D051697:Activating Transcription Factor 1; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020781:Matrix Metalloproteinase 1; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D051697:Activating Transcription Factor 1; D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D014157:Transcription Factors; D013004:Somatostatin; D017364:Collagenases; D020781:Matrix Metalloproteinase 1