HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/G96    most recent 00273.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Zeng, H. Articles by Neish, A. S. Search for Related Content PubMed PubMed Citation Articles by Zeng, H. Articles by Neish, A. S.

INFLAMMATION/IMMUNITY/MEDIATORS

Flagellin/TLR5 responses in epithelia reveal intertwined activation of inflammatory and apoptotic pathways

¹Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, and ²Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia

Submitted 15 June 2005 ; accepted in final form 15 September 2005

Flagellin, the primary structural component of bacterial flagella, is recognized by Toll-like receptor 5 (TLR5) present on the basolateral surface of intestinal epithelial cells. Utilizing biochemical assays of proinflammatory signaling pathways and mRNA expression profiling, we found that purified flagellin could recapitulate the human epithelial cell proinflammatory responses activated by flagellated pathogenic bacteria. Flagellin-induced proinflammatory activation showed similar kinetics and gene specificity as that induced by the classical endogenous proinflammatory cytokine TNF-, although both responses were more rapid than that elicited by viable flagellated bacteria. Flagellin, like TNF-, activated a number of antiapoptotic mediators, and pretreatment of epithelial cells with this bacterial protein could protect cells from subsequent bacterially mediated apoptotic challenge. However, when NF-B-mediated or phosphatidylinositol 3-kinase/Akt proinflammatory signaling was blocked, flagellin could induce programmed cell death. Consistently, we demonstrate that flagellin and viable flagellate Salmonella induces both the extrinsic and intrinsic caspase activation pathways, with the extrinsic pathway (caspase 8) activated by purified flagellin in a TLR5-dependant fashion. We conclude that interaction of flagellin with epithelial cells induces caspase activation in parallel with proinflammatory responses. Such intertwining of proinflammatory and apoptotic signaling mediated by bacterial products suggests roles for host programmed cell death in the pathogenesis of enteric infections.

Salmonella; inflammation; Toll-like receptor; cDNA microarray

This article has been cited by other articles:

				B. Fournier, I. R. Williams, A. T. Gewirtz, and A. S. Neish Toll-Like Receptor 5-Dependent Regulation of Inflammation in Systemic Salmonella enterica Serovar Typhimurium Infection Infect. Immun., September 1, 2009; 77(9): 4121 - 4129. [Abstract] [Full Text] [PDF]

				L. A. J. O'Neill, C. E. Bryant, and S. L. Doyle Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer Pharmacol. Rev., June 1, 2009; 61(2): 177 - 197. [Abstract] [Full Text] [PDF]

				B. Coburn, I. Sekirov, and B. B. Finlay Type III Secretion Systems and Disease Clin. Microbiol. Rev., October 1, 2007; 20(4): 535 - 549. [Abstract] [Full Text] [PDF]

				B. Salaun, S. Lebecque, S. Matikainen, D. Rimoldi, and P. Romero Toll-like Receptor 3 Expressed by Melanoma Cells as a Target for Therapy? Clin. Cancer Res., August 1, 2007; 13(15): 4565 - 4574. [Abstract] [Full Text] [PDF]

				W. Rodenburg, I. M. J. Bovee-Oudenhoven, E. Kramer, R. van der Meer, and J. Keijer Gene expression response of the rat small intestine following oral Salmonella infection Physiol Genomics, July 18, 2007; 30(2): 123 - 133. [Abstract] [Full Text] [PDF]

				C. Adriaensen, H. De Greve, J. Q. Tian, S. De Craeye, E. Gubbels, V. Eeckhaut, F. Van Immerseel, R. Ducatelle, M. Kumar, and J.-P. Hernalsteens A Live Salmonella enterica Serovar Enteritidis Vaccine Allows Serological Differentiation between Vaccinated and Infected Animals Infect. Immun., May 1, 2007; 75(5): 2461 - 2468. [Abstract] [Full Text] [PDF]

				A. S. Neish TLRS in the Gut. II. Flagellin-induced inflammation and antiapoptosis Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G462 - G466. [Abstract] [Full Text] [PDF]