| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Neuro-endocrine-immune axis is implicated in the pathophysiology of rheumatoid arthritis (EA). We here investigated roles of opioid peptides, endrophin and encephalin, and prolactin in the development of local lesions of EA. We revealed expression of opioid receptor μ and δ chains on RA synovial cell lines hy RT-PCR techniques and biding assay using radioisotopes. Introduction of opioid peptides into the RA synovial cell line culture resulted in suppressed proliferation and reduced production of inflammatory cytokines such as IL-1, TNF-α, IL-6, and ILr8. The effects were mediated by inhibition of the cyclic AMP signaling pathway, which was also shown to interfered with another neuropeptide, somatostatin as well as a specific, Rp-cAMP The cyclic AMP signaling pathway may be implicated in abnormal activation states of synovial cells in RA lesions, because immunohistochemical study showed abundant expression of cyclic AMP responsive element (CREB) in RA synovium. Therefore, the neuropeptides or their derivatives are possible therapeutic agents for RA. Agents, which modulate the production of the neuropetides, may be another options. In this study, we also found that prolactin stimulated RA synovial cell functions through the JAK2-STAT5 pathway, suggesting that the pathway is an alternative pharmacological target for RA therapy.Collectively, our current study provides important clues to develop novel drugs for RA on the basis of neuro-endocrine-immune axis.
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