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) A correction has been published 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 Wurfel, M. M. Articles by Martin, T. R. Search for Related Content PubMed PubMed Citation Articles by Wurfel, M. M. Articles by Martin, T. R.

Identification of High and Low Responders to Lipopolysaccharide in Normal Subjects: An Unbiased Approach to Identify Modulators of Innate Immunity ¹

Mark M. Wurfel^*, William Y. Park^*, Frank Radella^*, John Ruzinski^*, Andrew Sandstrom^*, Jeanna Strout^*, Roger E. Bumgarner and Thomas R. Martin^2,*

^* Medical Research Service, Veterans Affairs Puget Sound Medical Center and Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98105

LPS stimulates a vigorous inflammatory response from circulating leukocytes that varies greatly from individual to individual. The goal of this study was to use an unbiased approach to identify differences in gene expression that may account for the high degree of interindividual variability in inflammatory responses to LPS in the normal human population. We measured LPS-induced cytokine production ex vivo in whole blood from 102 healthy human subjects and identified individuals who consistently showed either very high or very low responses to LPS (denoted lps_high and lps_low, respectively). Comparison of gene expression profiles between the lps_high and lps_low individuals revealed 80 genes that were differentially expressed in the presence of LPS and 21 genes that were differentially expressed in the absence of LPS (p < 0.005, ANOVA). Expression of a subset of these genes was confirmed using real-time RT-PCR. Functional relevance for one gene confirmed to be expressed at a higher level in lps_high, adipophilin, was inferred when reduction in adipophilin mRNA by small interfering RNA in the human monocyte-like cell line THP-1 resulted in a modest but significant reduction in LPS-induced MCP-1 mRNA expression. These data illustrate a novel approach to the identification of factors that determine interindividual variability in innate immune inflammatory responses and identify adipophilin as a novel potential regulator of LPS-induced MCP-1 production in human monocytes.

This article has been cited by other articles:

				T. R. Martin Interactions between Mechanical and Biological Processes in Acute Lung Injury Proceedings of the ATS, April 15, 2008; 5(3): 291 - 296. [Abstract] [Full Text] [PDF]

				M. Hedl, J. Li, J. H. Cho, and C. Abraham Chronic stimulation of Nod2 mediates tolerance to bacterial products PNAS, December 4, 2007; 104(49): 19440 - 19445. [Abstract] [Full Text] [PDF]

				J. U. Raj, C. Aliferis, R. M. Caprioli, A. W. Cowley Jr., P. F. Davies, M. W. Duncan, D. J. Erle, S. C. Erzurum, P. W. Finn, H. Ischiropoulos, et al. Genomics and proteomics of lung disease: conference summary Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L45 - L51. [Full Text] [PDF]

				J. S. Lee, M. M. Wurfel, G. Matute-Bello, C. W. Frevert, M. R. Rosengart, M. Ranganathan, V. W. Wong, T. Holden, S. Sutlief, A. Richmond, et al. The Duffy Antigen Modifies Systemic and Local Tissue Chemokine Responses following Lipopolysaccharide Stimulation J. Immunol., December 1, 2006; 177(11): 8086 - 8094. [Abstract] [Full Text] [PDF]

				T. R. Martin and C. W. Frevert Innate Immunity in the Lungs Proceedings of the ATS, December 1, 2005; 2(5): 403 - 411. [Abstract] [Full Text] [PDF]