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: 291/4/L781    most recent 00031.2006v1 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 ISI 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 ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Fabisiak, J. P. Articles by Dauber, J. H. Search for Related Content PubMed PubMed Citation Articles by Fabisiak, J. P. Articles by Dauber, J. H.

Mycoplasma fermentans and TNF- interact to amplify immune-modulating cytokines in human lung fibroblasts

¹Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, and Departments of ⁴Medicine, and ³Cell Biology, University of Pittsburgh Graduate School of Public Health and College of Medicine, Pittsburgh, Pennsylvania; and ²Department of Medicine, University of California at Los Angeles, Los Angeles, California

Submitted 23 January 2006 ; accepted in final form 25 May 2006

Mycoplasma can establish latent infections and are associated with arthritis, leukemia, and chronic lung disease. We developed an experimental model in which lung cells are deliberately infected with Mycoplasma fermentans. Human lung fibroblasts (HLF) were exposed to live M. fermentans and immune-modulating cytokine release was assessed with and without known inducers of cytokine production. M. fermentans increased IL-6, IL-8/CXCL8, MCP-1/CCL2, and Gro-/CXCL1 production. M. fermentans interacted with TNF- to release more IL-6, CXCL8, and CXCL1 than predicted by the responses to either stimulus alone. The effects of live infection were recapitulated by exposure to M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a Toll-like receptor-2- and receptor-6-specific ligand. The synergistic effect of combined stimuli was more pronounced with prolonged incubations. Preexposure to TNF- sensitized the cells to subsequent MALP-2 challenge, but preexposure to MALP-2 did not alter the IL-6 response to TNF-. Exposure to M. fermentans or MALP-2 did not enhance nuclear localization, DNA binding, or transcriptional activity of NF-B and did not modulate early NF-B activation in response to TNF-. Application of specific inhibitors of various MAPKs suggested that p38 and JNK/stress-activated protein kinase were involved in early IL-6 release after exposure to TNF- and M. fermentans, respectively. The combined response to M. fermentans and TNF-, however, was uniquely sensitive to delayed application of SP-600125, suggesting that JNK/stress-activated protein kinase contributes to the amplification of IL-6 release. Thus M. fermentans interacts with stimuli such as TNF- to amplify lung cell production of immune-modulating cytokines. The mechanisms accounting for this interaction can now be dissected with the use of this in vitro model.

interleukin 6; chemokines; host defense; innate immunity; Toll-like receptors

This article has been cited by other articles:

				K. A. Brant and J. P. Fabisiak Nickel Alterations of TLR2-Dependent Chemokine Profiles in Lung Fibroblasts Are Mediated by COX-2 Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 591 - 599. [Abstract] [Full Text] [PDF]