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MR Vol.10 No.2 indexに戻る
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MODERN RHEUMATOLOGY
Vol.10 No.2 |
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Participation of substance P distribution in
the cytokine production of rheumatoid synovium |
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| H. Komuro1, T. Tanabe1, M. Ogushi1, S.
Takemura1, Y. Toda1, T. Morimoto1, S. Akagi1, R. Ogawa1 |
| (1)Department of Orthopaedic Surgery, Kansai
Medical University, 10-15 Fumizono, Moriguchi, Osaka 570-8507,
Japan |
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| Abstract |
| Abstract Based on findings which suggested the
involvement of the neuropeptide substance P in the pathogenesis of
rheumatoid arthritis (RA), we investigated the mechanism of synovial
pannus formation in RA, and examined the interaction between the
cytokine production of synovial tissues and the concentration of
substance P in the cartilage-pannus junction (CPJ). The CPJ and other
peripheral synovial tissues were separately obtained from each part
of the synovium from the knee joints of seven RA patients. The concentrations
of substance P and the cytokines interleukin (IL)-1# and IL-6 in
the CPJ and peripheral synovial tissues were determined by enzyme-linked
immunosorbent assays. In addition, synovial cells were isolated from
the CPJ and peripheral synovial tissues and treated with substance
P or neurokinin-1 receptor antagonist to analyze the changes in cytokine
production. The substance P levels were 211.2 and 50.5 pg/mg protein
in the CPJ and the peripheral synovium, respectively. The IL-1# and
IL-6 levels in the CPJ were 24.6 and 12.8 pg/mg protein, respectively.
In the peripheral synovium, these levels were 4.3 and 2.5 pg/mg protein,
respectively. In the CPJ, the IL-1# and IL-6 levels in tissue containing
a high concentration of substance P (>200 pg/mg protein) were
39.4 and 21.6 pg/mg protein, respectively, and those in tissue containing
a low concentration of substance P (h200 pg/mg protein) were 11.6
and 5.1 pg/mg protein, respectively. Synovial cells from the CPJ
produced higher levels of IL-1# and IL-6 than those from peripheral
tissues. In addition, treatment of the cells with an NK-1 antagonist
significantly reduced the production of these cytokines by the synovial
cells. The theory that substance P plays a role in the pathogenesis
of RA via the upregulation of cytokine production should be considered
in further studies on the immunomodulatory properties of substance
P in arthritis. |
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| Key words |
| Key words Cytokine production ・ Substance P ・ Synovial cells ・
Rheumatoid arthritis |
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