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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gorden, K. K. B. Articles by Alkan, S. S. Search for Related Content PubMed PubMed Citation Articles by Gorden, K. K. B. Articles by Alkan, S. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Cutting Edge: Activation of Murine TLR8 by a Combination of Imidazoquinoline Immune Response Modifiers and PolyT Oligodeoxynucleotides

Department of Pharmacology, 3M Pharmaceuticals, St. Paul, MN 55144

Synthetic immune response modifiers (IRM) such as imidazoquinolines can selectively activate human TLR7 or TLR8. Although these endosomal TLRs are close relatives, TLR7-deficient mice are unresponsive to TLR8 agonist IRMs. Similarly, natural ssRNA cannot activate murine TLR8, leading to the belief that murine TLR8 is nonfunctional. In this study, we transfected HEK293 cells with murine TLR8 and NF-B reporter constructs and stimulated them with combinations of IRM and oligodeoxynucleotides (ODNs). When stimulated with TLR7 or TLR8 agonists alone, no NF-B response was observed. However, a combination of polyT ODN plus the TLR8 agonist activated NF-B, whereas polyT ODN plus the TLR7 agonist did not activate. Primary mouse cells responded to the IRM/polyT ODN by secreting TNF. Cells from TLR7^–/– and TLR9^–/– mice responded to the IRM/polyT ODN combination, whereas MyD88^–/– cells did not respond. In conclusion, this study demonstrates for the first time that mouse TLR8 is functional.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Sefik S. Alkan, 3M Pharmaceuticals, 3M Center, 270-2S-06, St. Paul, MN 55144. E-mail address: ssalkan{at}mmm.com

² Abbreviations used in this paper: IRM, immune response modifier; ODN, oligodeoxynucleotide.

This article has been cited by other articles:

				A. Forsbach, J.-G. Nemorin, C. Montino, C. Muller, U. Samulowitz, A. P. Vicari, M. Jurk, G. K. Mutwiri, A. M. Krieg, G. B. Lipford, et al. Identification of RNA Sequence Motifs Stimulating Sequence-Specific TLR8-Dependent Immune Responses J. Immunol., March 15, 2008; 180(6): 3729 - 3738. [Abstract] [Full Text] [PDF]

				R. Dummer, A. Hauschild, J. C. Becker, J.-J. Grob, D. Schadendorf, V. Tebbs, J. Skalsky, K. C. Kaehler, S. Moosbauer, R. Clark, et al. An Exploratory Study of Systemic Administration of the Toll-like Receptor-7 Agonist 852A in Patients with Refractory Metastatic Melanoma Clin. Cancer Res., February 1, 2008; 14(3): 856 - 864. [Abstract] [Full Text] [PDF]

				P. Camateros, M. Tamaoka, M. Hassan, R. Marino, J. Moisan, D. Marion, M.-C. Guiot, J. G. Martin, and D. Radzioch Chronic Asthma-induced Airway Remodeling Is Prevented by Toll-like Receptor-7/8 Ligand S28463 Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1241 - 1249. [Abstract] [Full Text] [PDF]