title: Mitogen-activated protein kinase-dependent interleukin-1α intracrine signaling is modulated by YopP during Yersinia enterocolitica infection.
abstract: Yersinia enterocolitica is a food-borne pathogen that preferentially infects the Peyer'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-1α (IL-1α) was critical for the induction of gut inflammation characteristic of Y. enterocolitica infection. More recently, the known actions of IL-1α are becoming more complex because IL-1α 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-1α-dependent IL-8 production in epithelial cells. Nuclear translocation of pre-IL-1α protein and IL-1α-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-1α signaling. Infection of HeLa cells with a strain lacking the yopP gene resulted in increased nuclear translocation of pre-IL-1α and IL-1α-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-κB-dependent signal transduction pathways. Nuclear translocation of pre-IL-1α and IL-1α-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-κB. These data suggest that Y. enterocolitica inhibits intracellular pre-IL-1α signaling and subsequent proinflammatory responses through inhibition of MAP kinase pathways.
authors.affiliation: The University of Texas Health Science Center at San Antonio, Department of Microbiology and Immunology, San Antonio, Texas, USA.
authors.forename: Rumu
authors.initials: R
authors.lastname: Bose
authors.forename: Josephine
authors.initials: J
authors.lastname: Thinwa
authors.forename: Paola
authors.initials: P
authors.lastname: Chaparro
authors.forename: Youmin
authors.initials: Y
authors.lastname: Zhong
authors.forename: Santanu
authors.initials: S
authors.lastname: Bose
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Peter H
authors.initials: PH
authors.lastname: Dube
mesh_terms: D021581:Active Transport, Cell Nucleus; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D006367:HeLa Cells; D006801:Humans; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D053582:Interleukin-1alpha; D016209:Interleukin-8; D037521:Virulence Factors; C109227:YopP protein, Yersinia; D020928:Mitogen-Activated Protein Kinases
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