2011 Fiscal Year Final Research Report
Mechanism for the release of IL-8 from A549 cells treated with alpha-toxin.
| Project/Area Number |
21790431
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Tokushima Bunri University |
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Principal Investigator |
ODA Masataka 徳島文理大学, 薬学部, 講師 (00412403)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 病原性 |
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| Research Abstract |
A characteristic feature of gas gangrene with Clostridium perfringens(C. perfringens) is the absence of neutrophils within the infected area and the massive accumulation of neutrophils on the vascular endothelium at the margins. Intravenous injection of C. perfringens alpha-toxin into mice resulted in accumulation of neutrophils on the vascular endothelium in lung and liver, and release of GRO/KC. Alpha-toxin triggered activation of signal transduction pathways causing mRNA expression and production of IL-8, which activates migration and binding of neutrophils, in A549 cells. K252a, a tyrosine kinase A(TrkA) inhibitor, and siRNA for TrkA inhibited the toxin-induced phosphorylation of TrkA and production of IL-8.In addition, K252a inhibited the toxin-induced phosphorylation of ERK1/2 and p38 MAPK. PD98059, an ERK1/2 inhibitor, depressed phosphorylation of ERK1/2 and nuclear translocation of NF-κB p65, but SB203580, a p38 MAPK inhibitor, did not. On the other hand, PD98059 and SB203580 suppressed the toxin-induced production of IL-8.Treatment of the cells with PD98059 resulted in inhibition of IL-8 mRNA expression induced by the toxin and that with SB203580 led to a decrease in the stabilization of IL-8 mRNA. These results suggest that alpha-toxin induces production of IL-8 through the activation of two separate pathways, the ERK1/2/NF-κB and p38 MAPK pathways.
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