This Article Full Text Full Text (PDF) All Versions of this Article: 2005-0022OCv1 33/1/97    most recent 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van den Berg, A. Articles by Lutter, R. Search for Related Content PubMed PubMed Citation Articles by van den Berg, A. Articles by Lutter, R.

Interleukin-17 Induces Hyperresponsive Interleukin-8 and Interleukin-6 Production to Tumor Necrosis Factor- in Structural Lung Cells

Department of Pulmonology and Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam; and Departments of Pathology and Pulmonology, University of Groningen, Groningen, The Netherlands

Correspondence and requests for reprints should be addressed to Arjen van den Berg, AMC, Lab. Exp. Immunology, room G1-140, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: a.vandenberg{at}amc.uva.nl

Lung epithelial cells contribute to local inflammation by the production of pro-inflammatory mediators like interleukin (IL)-8 and IL-6. Although their production depends on gene transcription, previous studies showed that post-transcriptional mechanisms modulate IL-8 and IL-6 production. Human lung epithelial cells turn from normoresponsive into hyperresponsive IL-8– and IL-6–producing cells when their IL-8 and IL-6 mRNA degradation is reduced. We hypothesized that IL-17, a mediator predominantly released by memory T cells and present in airways of individuals with asthma, would modulate rather than induce IL-8 and IL-6 production by both human lung epithelial cells and fibroblasts. We show here for both cell types that IL-17 was a weak stimulus of IL-8 and IL-6 production, but markedly enhanced IL-8 and IL-6 responses to another stimulus, such as tumor necrosis factor-. This modulatory effect of IL-17 was paralleled by a reduced IL-8 and IL-6 mRNA degradation, with no effect on IL-8 and IL-6 gene transcription. In conclusion, IL-17 particularly affects post-transcriptional regulation of IL-8 and IL-6 expression leading to enhanced IL-8 and IL-6 responses to secondary stimuli, and is only a weak proinflammatory stimulus by itself. This poses the interesting concept that by releasing IL-17 from memory T cells, the adaptive immune system instructs lung structural cells as part of the innate immune system to respond more vigorously.

Key Words: chemokines • cytokines • inflammation • lung

This article has been cited by other articles:

				A. A. Shvedova, J. P. Fabisiak, E. R. Kisin, A. R. Murray, J. R. Roberts, Y. Y. Tyurina, J. M. Antonini, W. H. Feng, C. Kommineni, J. Reynolds, et al. Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 579 - 590. [Abstract] [Full Text] [PDF]

				S. Dragon, M. S. Rahman, J. Yang, H. Unruh, A. J. Halayko, and A. S. Gounni IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1023 - L1029. [Abstract] [Full Text] [PDF]

				I. Venza, M. Cucinotta, S. Caristi, G. Mancuso, and D. Teti Transcriptional Regulation of IL-8 by Staphylococcus aureus in Human Conjunctival Cells Involves Activation of AP-1 Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 270 - 276. [Abstract] [Full Text] [PDF]

				S. Henness, E. van Thoor, Q. Ge, C. L. Armour, J. M. Hughes, and A. J. Ammit IL-17A acts via p38 MAPK to increase stability of TNF-{alpha}-induced IL-8 mRNA in human ASM Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1283 - L1290. [Abstract] [Full Text] [PDF]

				S. Lajoie-Kadoch, P. Joubert, S. Letuve, A. J. Halayko, J. G. Martin, A. Soussi-Gounni, and Q. Hamid TNF-{alpha} and IFN-{gamma} inversely modulate expression of the IL-17E receptor in airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1238 - L1246. [Abstract] [Full Text] [PDF]

				M. I. Koenders, E. Lubberts, F. A. J. van de Loo, B. Oppers-Walgreen, L. van den Bersselaar, M. M. Helsen, J. K. Kolls, F. E. Di Padova, L. A. B. Joosten, and W. B. van den Berg Interleukin-17 Acts Independently of TNF-{alpha} under Arthritic Conditions J. Immunol., May 15, 2006; 176(10): 6262 - 6269. [Abstract] [Full Text] [PDF]

				R. Lutter and M. Spiteri Current perspectives in epithelial cell injury and repair: consequences for epithelial functions Eur. Respir. Rev., December 1, 2005; 14(97): 126 - 130. [Abstract] [Full Text] [PDF]