| Project/Area Number |
13670509
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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 |
Gastroenterology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
ISHIZUKA Yoshiyuki (2002) Shiga University of Medical Science, Medical Science, Assistant, 医学部, 助手 (80303775)
新谷 寛 (2001) 滋賀医科大学, 医学部, 助手 (80303767)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | hPFCs / Matrix metalloproteinase-1 / Cytokines / Intracellular signal trancduction / MAPK / PKC / Northern blot / Zymography / Matrix metalloproteienase-1 / Nortern blot / ヒト膵腺房由来Myofibroblast / Matrix metalloproteinases / シグナル伝達 / protein kinase C / MAP kinase / RT-PCR / Northern blotting |
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| Research Abstract |
We confirmed that matrix metalloproteinases(MMPs, MMP-1, 2, 9) were secreted from human pancreatic periacinar fibroblast-like cells(hPFCs) by gelatin gel zymography. A little amount of MMPs secretion were continuously observed in the absent of stimulants and that was remarkably enhanced in the presence of pro-inflammatory cytokines like IL-1β and TNF-α. Enhanced secretion induced by an application of IL-1β and TNF-α were reduced by an application of apigenin, a MAPK inhibitor and PD98059, a MEK inhibitor in a dose dependent manner, but not PKC inhihitor and SB203580, a p38 MAPK inhibitor.
It was demonstrated that PKC-independent and MEK dependent signaling pathways induced by pro-inflammatory cytokines were closely concerned with MMP-producing system by a northern blot analysis. The inhibitors of NF-κB(PTDC, TPCK) had no effect on MMP-1 mRNA expression induced by an application of pro-inflammatory cytokines, therefore it was suggested that PDTC and TPCK not blockable transcriptional factors could be worked. Taken together, it resulted that pro-inflammatory cytokines stimulated MMPs production from hPFCs via some regulatory mechanisms involving MEK related signaling path ways.
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