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 Stankova, J. Articles by Rola-Pleszczynski, M. Search for Related Content PubMed PubMed Citation Articles by Stankova, J. Articles by Rola-Pleszczynski, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL DACTINOMYCIN DEXAMETHASONE

Modulation of Leukotriene B₄ Receptor-1 Expression by Dexamethasone: Potential Mechanism for Enhanced Neutrophil Survival¹

Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Glucocorticoids can down-regulate many inflammatory and immune responses and constitute a powerful therapeutic tool in a number of diseases. However, they have a somewhat paradoxical effect on neutrophils, in that they prolong their survival. Because leukotriene B₄ (LTB₄) can also extend neutrophil survival, we proposed that glucocorticoids could prevent neutrophil apoptosis by up-regulating their expression of the high-affinity LTB₄ receptor (BLT1). Here we show that, indeed, dexamethasone (DEX) up-regulates the steady-state levels of BLT1 mRNA in human neutrophils. The effect was time and concentration dependent, being maximal at 4 h and at 10–100 nM DEX. The effect was also dependent on transcriptional activity, whereas BLT1 mRNA stability was not affected. DEX-induced up-regulation of BLT1 expression was prevented by pretreatment with the LTB₄ antagonist LY255283. Moreover, LTB₄ itself up-regulated the expression of BLT1 mRNA. BLT1 protein expression on neutrophils exposed to DEX for 24 h was also up-regulated 2- to 3-fold, and DEX-treated as well as LTB₄-treated cells showed enhanced responsiveness to LTB₄ in terms of intracellular Ca²⁺ mobilization and chemotaxis. Whereas DEX and LTB₄ alone decreased neutrophil apoptosis by 50%, neutrophils treated with both LTB₄ and DEX showed >90% survival at 24 h. Moreover, BLT1 antagonists prevented the increased neutrophil survival induced by DEX as well as by LTB₄. Taken together, our results suggest that DEX-induced up-regulation of BLT1 expression in neutrophils may be one mechanism through which glucocorticoids can prolong neutrophil survival, namely by enhancing cell responses to the antiapoptotic effect of LTB₄.

This article has been cited by other articles:

				M. Peters-Golden and W. R. Henderson Jr. Leukotrienes N. Engl. J. Med., November 1, 2007; 357(18): 1841 - 1854. [Full Text] [PDF]

				H. Qiu, A.-S. Johansson, M. Sjostrom, M. Wan, O. Schroder, J. Palmblad, and J. Z. Haeggstrom Differential induction of BLT receptor expression on human endothelial cells by lipopolysacharide, cytokines, and leukotriene B4 PNAS, May 2, 2006; 103(18): 6913 - 6918. [Abstract] [Full Text] [PDF]

				A. Pettersson, A. Sabirsh, J. Bristulf, K. Kidd-Ljunggren, B. Ljungberg, C. Owman, and U. Karlsson Pro- and anti-inflammatory substances modulate expression of the leukotriene B4 receptor, BLT1, in human monocytes J. Leukoc. Biol., June 1, 2005; 77(6): 1018 - 1025. [Abstract] [Full Text] [PDF]

				E. Gaudreault, C. Thompson, J. Stankova, and M. Rola-Pleszczynski Involvement of BLT1 Endocytosis and Yes Kinase Activation in Leukotriene B4-Induced Neutrophil Degranulation J. Immunol., March 15, 2005; 174(6): 3617 - 3625. [Abstract] [Full Text] [PDF]

				M. Back, H. Qiu, J. Z. Haeggstrom, and K. Sakata Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H419 - H424. [Abstract] [Full Text] [PDF]