Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Oda, Masataka¹  Shiihara, Ryota¹  Ohmae, Yuka¹  Kabura, Michiko¹  Takagishi, Teruhisa¹  Kobayashi, Keiko¹  Nagahama, Masahiro¹  Sakurai, Jun¹ 

[1] Tokushima Bunri Univ, Fac Pharmaceut Sci, Dept Microbiol, Yamashiro, Tokushima 7708514, Japan

关键词: Alpha-toxin;    A549 cell;    TrkA;    IL-8;    ERK1/2;    p38 MAPK;   

DOI  :  10.1016/j.bbadis.2012.06.007

来源: Elsevier

【 摘 要 】

A characteristic feature of gas gangrene with Clostridium petfringens (C petfringens) is the absence of neutrophils within the infected area and the massive accumulation of neutrophils at the vascular endothelium around the margins of the necrotic region. Intravenous injection of C petfringens alpha-toxin into mice resulted in the accumulation of neutrophils at the vascular endothelium in lung and liver, and release of GRO/KC a member of the CXC chemokine family with homology to human interleukin-8 (IL-8). 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 extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). PD98059, an ERK1/2 inhibitor, depressed phosphorylation of ERK1/2 and nuclear translocation of nuclear factor kappa B (NF-kappa B) 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-kappa B and p38 MAPK pathways. Published by Elsevier B.V.

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