Mitogen-Activated Protein Kinase-Dependent Interleukin-1 alpha Intracrine Signaling Is Modulated by YopP during Yersinia enterocolitica Infection

作者：Bose Rumu; Thinwa Josephine; Chaparro Paola; Zhong Youmin; Bose Santanu; Zhong Guangming; Dube Peter H^*

来源：Infection and Immunity, 2012, 80(1): 289-297.

DOI：10.1128/IAI.05742-11

Yersinia enterocolitica is a food-borne pathogen that preferentially infects the Peyer%26apos;s patches and mesenteric lymph nodes, causing an acute inflammatory reaction. Even though Y. enterocolitica induces a robust inflammatory response during infection, the bacterium has evolved a number of virulence factors to limit the extent of this response. We previously demonstrated that interleukin-1 alpha (IL-1 alpha) was critical for the induction of gut inflammation characteristic of Y. enterocolitica infection. More recently, the known actions of IL-1 alpha are becoming more complex because IL-1 alpha can function both as a proinflammatory cytokine and as a nuclear factor. In this study, we tested the ability of Y. enterocolitica to modulate intracellular IL-1 alpha-dependent IL-8 production in epithelial cells. Nuclear translocation of pre-IL-1 alpha protein and IL-1 alpha-dependent secretion of IL-8 into the culture supernatant were increased during infection with a strain lacking the 70-kDa virulence plasmid compared to the case during infection with the wild type, suggesting that Yersinia outer proteins (Yops) might be involved in modulating intracellular IL-1 alpha signaling. Infection of HeLa cells with a strain lacking the yopP gene resulted in increased nuclear translocation of pre-IL-1 alpha and IL-1 alpha-dependent secretion of IL-8 similar to what is observed with bacteria lacking the virulence plasmid. YopP is a protein acetylase that inhibits mitogen-activated protein kinase (MAP kinase)- and NF-kappa B-dependent signal transduction pathways. Nuclear translocation of pre-IL-1 alpha and IL-1 alpha-dependent secretion of IL-8 in response to Yersinia enterocolitica infection were dependent on extracellular signal-regulated kinase (ERK) and p38 MAP kinase signaling but independent of NF-kappa B. These data suggest that Y. enterocolitica inhibits intracellular pre-IL-1 alpha signaling and subsequent proinflammatory responses through inhibition of MAP kinase pathways.

• 出版日期2012-1