| Project/Area Number |
15590819
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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 |
TAKAHASHI Hiroki Sapporo Medical University, School of Med, Associate Prof, 医学部, 助教授 (60231396)
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| Co-Investigator(Kenkyū-buntansha) |
KUORKI Yoshio Sapporo Medical University, School of Med, Professor, 医学部, 教授 (70161784)
SHIRATORI Masanori Sapporo Medical University, School of Med, Assistant Prof, 医学部, 講師 (40295366)
CHIBA Hirofumi Sapporo Medical University, School of Med, Instructor, 医学部, 助手 (40347175)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | interstitial pneumonia / surfactant protein A / Toll-like receptor / alveolar macrophage / Staphylococcus aureus / peptidoglycan / Mycoplasma pneumoniae / lipoprotein / 肺サーファクタント蛋白質 / SP-A / Toll-like receptor / TNF-α |
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| Research Abstract |
Chronic Interstitial pneumonias involve a group showing poor prognosis including idiopathic pulmonary fibrosis (IPF). Patients with IPF occasionally complicate with infection-triggered exacerbation of respiratory disturbance and result in death. Pathologic feature of the exacerbation is diffuse alveolar damage and its molecular biology is of the basis of the upregulation of bioactive materials presented by TNF-a. Therefore, to inhibit the upregulation of TNF-a in the patients' lungs may prevent the exacerbation and then bring a good survival rate. The expression of TNF-a is upregulated by the interaction with various bacterial components and Toll-like receptor (TLR) expressed in cell membrane of inflammatory immune cells. On the other hand, surfactant protein (SP)-A is known to provide an inhibitory effect on the inflammatory reaction in vitro.
We firstly investigated whether SP-A alters cellular responses by Staphylococcus aureus derived peptidoglycan (PGN). The inhibitory effect on TNF-a secretion was dependent upon SP-A concentrations in physiological range. SP-A. directly bound to a soluble form of the recombinant extracellular TLR2 domain (sTLR2). Coincubation of sTLR2 with SP-A significantly reduced the binding of sTLR2 to PGN. These results indicate that the direct interaction of SP-A with TLR2 alters PGN-induced cell signaling. We next studied interaction between SP-A and, Mycoplasma pneumoniae. SP-A enhanced the action of the lipoprotein prepared from the pathogen, increasing the release of TNF-a and NO. Only cells transfected with TLR2 or CD 14 plus TLR2 produced TNF-a. These findings directly implicate SP-A, CD 14 and TLR2 in the immediate innate response to M. pneumoniae.
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