2002 Fiscal Year Final Research Report Summary
Investigation of induction of Th1 cytokines by osteopontin in granulomatous lung diseases
| Project/Area Number |
13670608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
CHIBA Hirofumi Sapporo Medical University School of Medicine, Third Department of Internal medicine, Instructor, 医学部, 助手 (40347175)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Gen Sapporo Medical University School of Medicine, Third Department of Internal medicine, Assistant Professor, 医学部, 講師 (70315505)
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| Project Period (FY) |
2001 – 2002
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| Keywords | osteopontin / Th1 cytokine / sarcoidosis |
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| Research Abstract |
Osteopontin (OPN) is a secreted arginine grycine aspartate containing noncollagenous matrix protein associated with T helper type 1 (Th1) granulomatous responses. We measured OPN (full-length and cleaved forms) in plasma and bronchoalveolar lavage (BAL) fluids in tuberculosis and sarcoidosis as well as Th1 cytokines including mterferon-γ(IFN-γ), interleukin-12 (IL-12) and IL-18. Levels of full-length OPN well correlated with levels of thrombin cleaved forms of OPN, indicating little cleavage of OPN in plasma. Western blotting also showed that major bands were full-length OPN. Significantly increased levels of circulating OPN were observed in patients with pulmonary tuberculosis and sarcoidosis as compared with healthy controls. The levels of circulating OPN paralleled the extent of lung lesions evaluated on chest X ray films and magnitude of fever in pulmonary tuberculosis. Thrombin-cleaved OPN levels were significantly increased in BAL fluid of sarcoidosis. Circulating full-length OPN levels correlated with BAL fluid thrombin-cleaved OPN levels in sarcoidosis. Circulating OPN levels correlated with circulating IFN-γ, IL-12 and IL-18 levels in tuberculosis. With anti-tuberculous therapy, circulating OPN levels were significantly decreased in parallel with the improvement of symptoms and chest X-ray findings. Plasma OPN may reflect disease severity and the grade of Th1 responses in granulomatous lung diseases especially tuberculosis. We sought OPN single nucleotide polymorphisms (SNP) analyzing systems in patients with sarcoidosis and pulmonary tuberculosis in whom informed content was obtained. We established OPN SNP analyzing systems at 443 and 616 base pair upstream from the transcription initiation site (promoter region).
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