2002 Fiscal Year Final Research Report Summary
Investigation of regulation of Th1 cytokine production by Clara cell 10-kDa protein in granulomatous lung diseases
| Project/Area Number |
13670610
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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 |
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 | CC10 / Th1 cytokine / sarcoidosis / secretoglobin |
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| Research Abstract |
Clara cell 10-kDa protein (CC10) is the predominant product from non-ciliated bronchiolar epithelial cells (Clara cells). Human CC10 is encoded by a three kilo-base (kb) single-copy gene, which contains three exons and two introns and is localized in the long arm of chromosome 11 (11q12.3-q13.1) CC10 is a homodimer of polypeptide of 70 amino acids covalently bound in an anti-parallel manner. CC10 has been proven to be identical with uteroglobin and protein 1. CC10 possesses aniti-inflmamatory function and inhibits interferon-γ function. CC10 forms one of intra- and intercellular regulators involved in inflammation and malignant transformation in the respiratory fields.
We investigated single nucleotide polymorphisms (SNPs) of CC10 gene, showing 6 different SNPs. We analyzed guanine-adenine substitution at position 38 (G38A) downstream from the transcription initiation site in patients with sarcoidosis by allele specific PCR and compared clinical parameters and CC10 levels in serum and bronchoalveolar lavage (BAL) fluid among three genotypes. The A allele frequency in sarcoidosis was significantly higher than that of healthy controls. There were no significant differences of gender, ages, distributions of radiogiaphic stages, number of affected organs, ACE activities, or data of BAL examinations among the genotype groups. However, the A/A genotype group had significant greater rates of disease progression compared with the G/G and G/A genotype groups. The A/A genotype group had significantly lower CC10 levels in serum and BAL fluid compared with the G/G and G/A genotype groups. In the reporter gene assay, significantly lower luciferase reporter activities were detected for the 38A construct compared with the 38G construct in the presence of interferon-γ, but not in the absence of interferon-γ. CC10 G38A SNP may influence CC10 protein expression and be associated with disease progression of sarcoidosis.
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Research Products
(12 results)
