| Project/Area Number |
14570200
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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 |
Experimental pathology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
KUMASAKA Toshio Juntendo University, School of Medicine, Assistant professor, 医学部, 講師 (00286709)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDO Kazumi Tokushima Bunri Univ., Health Science Institute, Professor, 健康科学研究所, 教授 (40212906)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hermansky-Pudlak syndrome / HPS-1 / Pale ear / ep / Silica / Procollagen mRNA / Transforming growth factor-beta / 肺線維症 / Procollagen mRNAs / 胎児線維芽細胞 / Real time RT-PCR / TGF-beta / Hermansky-Pudlak症候群 / ep遺伝子 / Cathepsin L / Lysosome / 免疫電顕 / 胎児線維芽細胞株 |
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| Research Abstract |
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet dysfunction, and ceroid storage pool disease, as well as a high incidence of pulmonary fibrosis later in life. Pale ear, a mouse model of HPS, is similar in phenotype but lung fibrosis has not been described. This study examined the susceptibility of Pale ear mice to pulmonary fibrosis induced by intratracheal instillation of silica. The results show that in the early phase (days 1-7) inflammatory cell influx and protein exudate in the broncho-alveolar fluid were less in Pale ear compared to wild type mice. Granuloma formation in the lung parenchyma was also less in Pale ear mice. In the late phase (days7-56), the lymphocyte accumulation in the lung was increased in the lung interstitium of Pale ear mice. Expression of procollagen type III mRNA was less in the early phase, while expression of procollagen type I mRNA was greater in the late phase in Pale ear compared to wild type mice. Gene microarrays showed that expression of the cytokine mRNA for interleukin-1β, macrophage inflammatory protein-1β, 2 and tumor necrosis factor-α were a half to a third lower than the levels showed in Pale ear mice compared with wild type mice on day 7. On day 56, the expression of cytokine mRNAs was similar, but transforming growth factor-β was increased 1.8-fold in Pale ear mice to compare in wild type. Thus, in response to silica, Pale ear mice have a defect in the Pale ear mice inflammatory response including granuloma formation in the early phase but greater procollagen type I mRNA expression in the lungs and a greater recruitment of lymphocytes in the later stage compared with wild type mice.
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