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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, M. Articles by Liew, F. Y. Search for Related Content PubMed PubMed Citation Articles by Patel, M. Articles by Liew, F. Y. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

TLR2 Agonist Ameliorates Established Allergic Airway Inflammation by Promoting Th1 Response and Not via Regulatory T Cells¹

Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, Scotland, United Kingdom

TLRs are primary sensors of both innate and adaptive immune systems, where they play a pivotal role in the response directed against structurally conserved components of pathogens. Synthetic bacterial lipopeptide Pam3CSK4 is a TLR2 agonist capable of modulating Th1 and Th2 responses. This study examines the therapeutic effect of Pam3CSK4 in established airway inflammation in a murine model of asthma. In mice previously sensitized and challenged with OVA, Pam3CSK4 given i.p. markedly reduced the total inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid. Pam3CSK4 therapy was associated with a reduction in OVA-induced IL-4 and IL-5 secretion from thoracic lymph node culture, airways inflammation, bronchial hyperresponsiveness, and serum levels of IgE. Pam3CSK4 therapy was also associated with an increase in OVA-induced IFN-, IL-12, and IL-10 production. However, the anti-inflammatory effect of Pam3CSK4 was independent of IL-10 or TGF-, but was critically dependent on IL-12, the production of which by dendritic cells was enhanced by Pam3CSK4 in vitro. Our results provide direct evidence that Pam3CSK4 could represent a novel therapeutic agent in allergic airways disease.

This article has been cited by other articles:

				M. Kurowska-Stolarska, B. Stolarski, P. Kewin, G. Murphy, C. J. Corrigan, S. Ying, N. Pitman, A. Mirchandani, B. Rana, N. van Rooijen, et al. IL-33 Amplifies the Polarization of Alternatively Activated Macrophages That Contribute to Airway Inflammation J. Immunol., November 15, 2009; 183(10): 6469 - 6477. [Abstract] [Full Text] [PDF]

				K. Page, J. R. Ledford, P. Zhou, and M. Wills-Karp A TLR2 Agonist in German Cockroach Frass Activates MMP-9 Release and Is Protective against Allergic Inflammation in Mice J. Immunol., September 1, 2009; 183(5): 3400 - 3408. [Abstract] [Full Text] [PDF]

				C. S. McKimmie, M. Moore, A. R. Fraser, T. Jamieson, D. Xu, C. Burt, N. I. Pitman, R. J. Nibbs, I. B. McInnes, F. Y. Liew, et al. A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration Blood, April 30, 2009; 113(18): 4224 - 4231. [Abstract] [Full Text] [PDF]

				C. A. Da Silva, C. Chalouni, A. Williams, D. Hartl, C. G. Lee, and J. A. Elias Chitin Is a Size-Dependent Regulator of Macrophage TNF and IL-10 Production J. Immunol., March 15, 2009; 182(6): 3573 - 3582. [Abstract] [Full Text] [PDF]

				M. Kurowska-Stolarska, P. Kewin, G. Murphy, R. C. Russo, B. Stolarski, C. C. Garcia, M. Komai-Koma, N. Pitman, Y. Li, A. N. J. McKenzie, et al. IL-33 Induces Antigen-Specific IL-5+ T Cells and Promotes Allergic-Induced Airway Inflammation Independent of IL-4 J. Immunol., October 1, 2008; 181(7): 4780 - 4790. [Abstract] [Full Text] [PDF]

				T. Yokoi, R. Amakawa, T. Tanijiri, H. Sugimoto, Y. Torii, H. Amuro, Y. Son, K. Tajima, Y.-J. Liu, T. Ito, et al. Mycobacterium bovis Bacillus Calmette-Guerin suppresses inflammatory Th2 responses by inducing functional alteration of TSLP-activated dendritic cells Int. Immunol., October 1, 2008; 20(10): 1321 - 1329. [Abstract] [Full Text] [PDF]

				K. Page, K. M. Lierl, V. S. Hughes, P. Zhou, J. R. Ledford, and M. Wills-Karp TLR2-Mediated Activation of Neutrophils in Response to German Cockroach Frass J. Immunol., May 1, 2008; 180(9): 6317 - 6324. [Abstract] [Full Text] [PDF]

				D. Yang, Q. Chen, S. B. Su, P. Zhang, K. Kurosaka, R. R. Caspi, S. M. Michalek, H. F. Rosenberg, N. Zhang, and J. J. Oppenheim Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses J. Exp. Med., January 21, 2008; 205(1): 79 - 90. [Abstract] [Full Text] [PDF]

				Y. Yanagawa and K. Onoe Enhanced IL-10 Production by TLR4- and TLR2-Primed Dendritic Cells upon TLR Restimulation J. Immunol., May 15, 2007; 178(10): 6173 - 6180. [Abstract] [Full Text] [PDF]

				Q. Wu, R. J. Martin, J. G. Rino, S. Jeyaseelan, R. Breed, and H. W. Chu A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1064 - L1072. [Abstract] [Full Text] [PDF]

				J. Sun and E. J. Pearce Suppression of Early IL-4 Production Underlies the Failure of CD4 T Cells Activated by TLR-Stimulated Dendritic Cells to Differentiate into Th2 Cells J. Immunol., February 1, 2007; 178(3): 1635 - 1644. [Abstract] [Full Text] [PDF]

				X. Shan, A. Hu, H. Veler, S. Fatma, J. S. Grunstein, S. Chuang, and M. M. Grunstein Regulation of Toll-like receptor 4-induced proasthmatic changes in airway smooth muscle function by opposing actions of ERK1/2 and p38 MAPK signaling Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L324 - L333. [Abstract] [Full Text] [PDF]

				H. J. Brown, S. H. Sacks, and M. G. Robson Toll-Like Receptor 2 Agonists Exacerbate Accelerated Nephrotoxic Nephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1931 - 1939. [Abstract] [Full Text] [PDF]