1993 Fiscal Year Final Research Report Summary
The roles of cytokines in pulmonary fibrosis
| Project/Area Number |
04670469
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Tokushima, School of Medicine |
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Principal Investigator |
OGUSHI Fumitaka Third Departmant of Internal Medicine, University of Tokushima, School of Medicine, 医学部・附属病院, 講師 (80201375)
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| Co-Investigator(Kenkyū-buntansha) |
SONE Saburo Third Departmant of Internal Medicine, Tokushima University, School of Medicine, 医学部, 助教授 (40145024)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Pulmonary Fibrosis / Cell-associated IL-1 / Fibroblast / IL-4 / Prostaglandin E2 / Cyclooxygenase / TNF |
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| Research Abstract |
In order to clarify the machanisms of pulmonary fibrosis, we examined theprodiction of interleukin-1(IL-1) of alveolar machrophges (AM) from bleomycin(BLM)-induced pulmonary fibrosis in rats. Extracellular IL-1 was detected in culture media of AM at only day 1 after administration of BLM.On the other hand, cell-associated IL-1 was detected in AM fixed by paraformaldehyde on days 1, 3, 6 and 9 after administration of BLM.Cell accociated IL-1 was neutralized by treatment of anti IL-1 alpha antibody and was not neutralized by treatment of anti IL-1 beta antibody. The cell associated IL-1 inhibited proliferation of fibroblast, and the inhibition of fibroblasts was neutralized by anti IL-1 alpha antibody. these results suggested that cell-associated IL-1 might play an important roles in pulmonary fibrosis. Then, growth rate of fibroblasts obtained from BLM-treated rats was compared with those obtained from control rats. Proliferation of fibroblasts obtained from BLM-treated rats at 4 days after BLM instillation was significantly faster than that of control. Next, we investigated the regulatory mechanisms of cytokine production by alveolar macrophages(AM) and monocytes. IL-4 suppressed the production of IL-1, IL-6 and TNFalpha by activated AM and monocyte. Onthe ather hand, the production of IL-1, receptor antagonist, which specifically blocis IL-1 at its receptor level was up-regulated by IL-4. We supposed that interaction between AM and fibroblasts in situ was important in pulmonary diseases. Fibroblasts were stimulated with IL-1 and TNF and IL-8 was detected in culture media. II which is enzyme to synthesis of PGE2 increased. PGE2 production from fibroblasts were inhibited by IL-4.
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Research Products
(15 results)
