This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kampik, D. Articles by Autenrieth, I. B. Search for Related Content PubMed PubMed Citation Articles by Kampik, D. Articles by Autenrieth, I. B.

 Previous Article  |  Next Article 

Infection and Immunity, May 2000, p. 2484-2492, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Yersinia enterocolitica Invasin Protein Triggers Differential Production of Interleukin-1, Interleukin-8, Monocyte Chemoattractant Protein 1, Granulocyte-Macrophage Colony-Stimulating Factor, and Tumor Necrosis Factor Alpha in Epithelial Cells: Implications for Understanding the Early Cytokine Network in Yersinia Infections

Daniel Kampik, Ralf Schulte, and Ingo B. Autenrieth^*

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, Munich, Germany

Received 14 December 1999/Returned for modification 18 January 2000/Accepted 1 February 2000

Yersinia enterocolitica infection of epithelial cells results in interleukin-8 (IL-8) mRNA expression. Herein we demonstrate that besides IL-8, increased mRNA levels of five other cytokines, IL-1, IL-1, monocyte chemoattractant protein 1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-), can be detected upon infection of HeLa cells with Yersinia. Yersinia-triggered cytokine production was not affected by blocking phosphatidylinositol-3-phosphate kinase with wortmannin, which inhibited bacterial invasion. Comparable cytokine mRNA responses were triggered by Escherichia coli expressing Yersinia inv, while no response was triggered by an inv-deficient Yersinia mutant. Moreover, cytokine responses were independent from metabolic activity of the bacteria, as killed bacterial cells were sufficient for triggering cytokine responses in HeLa cells. Semiquantitative reverse transcription-PCR analysis was used to assess the kinetics of cytokine mRNA expression in infected HeLa cells. IL-8, IL-1, IL-1, MCP-1, GM-CSF, and TNF- mRNA expression increased within 1 h postinfection, reached a maximum after 3 to 4 h, and then declined to preinfection levels within 3 h. IL-8, MCP-1, and GM-CSF were secreted by HeLa cells, whereas IL-1 and IL-1 were not secreted and thus were found exclusively intracellularly. TNF- protein could not be detected in cell lysates or supernatants. Stimulation of HeLa cells with IL-1 was followed by increased IL-8 mRNA expression, whereas stimulation with IL-8 did not induce cytokine production. Likewise, MCP-1 and GM-CSF did not induce significant cytokine responses in HeLa cells. Our results implicate that the initial host response to Yersinia infection might be sustained by IL-8, MCP-1, and GM-CSF produced by epithelial cells.

---

^* Corresponding author. Mailing address: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig Maximilians-Universität, Pettenkoferstrasse 9a, D-80336 Munich, Germany. Phone: 49-89-51605280. Fax: 49-89-51605223. E-mail: Autenrieth{at}m3401.mpk.med.uni-muenchen.de.

---

Infection and Immunity, May 2000, p. 2484-2492, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Frick, J. S., Fink, K., Kahl, F., Niemiec, M. J., Quitadamo, M., Schenk, K., Autenrieth, I. B. (2007). Identification of Commensal Bacterial Strains That Modulate Yersinia enterocolitica and Dextran Sodium Sulfate-Induced Inflammatory Responses: Implications for the Development of Probiotics. Infect. Immun. 75: 3490-3497 [Abstract] [Full Text]  
• McNally, A., La Ragione, R. M., Best, A., Manning, G., Newell, D. G. (2007). An aflagellate mutant Yersinia enterocolitica biotype 1A strain displays altered invasion of epithelial cells, persistence in macrophages, and cytokine secretion profiles in vitro. Microbiology 153: 1339-1349 [Abstract] [Full Text]  
• McNally, A., Dalton, T., Ragione, R. M. L., Stapleton, K., Manning, G., Newell, D. G. (2006). Yersinia enterocolitica isolates of differing biotypes from humans and animals are adherent, invasive and persist in macrophages, but differ in cytokine secretion profiles in vitro.. J Med Microbiol 55: 1725-1734 [Abstract] [Full Text]  
• Schmid, Y., Grassl, G. A., Buhler, O. T., Skurnik, M., Autenrieth, I. B., Bohn, E. (2004). Yersinia enterocolitica Adhesin A Induces Production of Interleukin-8 in Epithelial Cells. Infect. Immun. 72: 6780-6789 [Abstract] [Full Text]  
• Dube, P. H., Handley, S. A., Lewis, J., Miller, V. L. (2004). Protective Role of Interleukin-6 during Yersinia enterocolitica Infection Is Mediated through the Modulation of Inflammatory Cytokines. Infect. Immun. 72: 3561-3570 [Abstract] [Full Text]  
• Berkes, J, Viswanathan, V K, Savkovic, S D, Hecht, G (2003). Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut 52: 439-451 [Abstract] [Full Text]  
• Cottet, S., Corthesy-Theulaz, I., Spertini, F., Corthesy, B. (2002). Microaerophilic Conditions Permit to Mimic in Vitro Events Occurring during in Vivo Helicobacter pylori Infection and to Identify Rho/Ras-associated Proteins in Cellular Signaling. J. Biol. Chem. 277: 33978-33986 [Abstract] [Full Text]  
• Werner, E., Kheradmand, F., Isberg, R. R., Werb, Z. (2002). Phagocytosis mediated by Yersinia invasin induces collagenase-1 expression in rabbit synovial fibroblasts through a proinflammatory cascade. J. Cell Sci. 114: 3333-3343 [Abstract] [Full Text]  
• Isberg, R., Barnes, P (2001). Subversion of integrins by enteropathogenic Yersinia. J. Cell Sci. 114: 21-28 [Abstract]