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Published online before print March 12, 2004

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© 2004 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1103589

Received for publication November 25, 2003.
Revised January 27, 2004.
Accepted for publication February 9, 2004.

Article

Estrogen receptor- deficiency promotes increased TNF- secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro

K. Chad Lambert ^*, Edward M. Curran , Barbara M. Judy , Dennis B. Lubahn , and D. Mark Estes ^*@

Departments of *Molecular Microbiology & Immunology and Biochemistry and Center for Phytonutrient and Phytochemical Research, University of Missouri, Columbia; and University of Texas Medical Branch, Department of Pediatrics, Sealy Center for Vaccine Development, Galveston

^@ To whom correspondence should be addressed. E-mail: dmestes{at}utmb.edu.

	Abstract

In this series of studies, we determined the potential role of intracellular estrogen receptors (ER), ER and ER, on macrophage function in response to bacterial stimuli. The sex hormone 17-estradiol (E₂) and ER have been shown to modulate inflammatory responses as well as T helper cell type 1 (TH1)/TH2 responses. The mechanisms E₂ and its receptors use to alter these immune functions remain largely unknown. ER and ER possess complex actions in tissue where they are expressed. We have characterized the receptor repertoire of murine dendritic cells and thioglycollate-elicited peritoneal macrophages (PM). Both cell types express mRNA for ER. Neither cell type expressed detectable amounts of ER mRNA, as determined by reverse transcriptase-polymerase chain reaction using exon-specific primers spanning each of the seven intron/exon junctions. Primary macrophages from ER- and ER-deficient severe combined immunodeficiency mice [ER knockout (KO) and ERßKO, respectively] were used to delineate the effects and potential mechanisms via which steroid receptors modulate macrophage function. ER-deficient PM exposed ex vivo to lipopolysaccharide or Mycobacterium avium exhibited significant increases in tumor necrosis factor (TNF-) secretion as well as reduction in bacterial load when compared with wild-type (WT) PM. In contrast, ER-deficient PM possessed no significant difference in TNF- secretion or in bacterial load when compared with WT littermates. These studies suggest that ER, but not ER, modulates murine PM function.

Key Words: SERMS • inflammation • NF-B • hormone-independent

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