Abstract |
Regulation of the inflammatory response is imperative to the maintenance of immune homeostasis. Activated monocytes elaborate a broad variety of proinflammatory cytokines that mediate inflammation, including CXCL8. Release of this chemokine attracts neutrophils to sites of bacterial invasion and inflammation; however, high levels of CXCL8 may result in excessive neutrophil infiltration and subsequent tissue damage. In this study, we demonstrate that 17beta-estradiol (E2) attenuates LPS-induced expression of CXCL8 in human peripheral blood monocytes. Treatment of monocytes with estradiol before administration of LPS reduces CXCL8 message and protein production through an estrogen receptor-dependent mechanism, and luciferase reporter assays demonstrate that this inhibition is mediated transcriptionally. Importantly, the ability of estradiol-pretreated LPS-activated monocytes to mobilize neutrophils is impaired. These results implicate a role for estradiol in the modulation of the immune response, and may lead to an enhanced understanding of gender-based differences in inflammatory control mechanisms.
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Authors | Patricia A Pioli, Amy L Jensen, Lehn K Weaver, Eyal Amiel, Zheng Shen, Li Shen, Charles R Wira, Paul M Guyre |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 179
Issue 9
Pg. 6284-90
(Nov 01 2007)
ISSN: 0022-1767 [Print] United States |
PMID | 17947704
(Publication Type: Journal Article)
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Chemical References |
- Interleukin-8
- Lipopolysaccharides
- TLR4 protein, human
- Toll-Like Receptor 4
- Estradiol
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Topics |
- Cells, Cultured
- Endoplasmic Reticulum
(drug effects, metabolism)
- Estradiol
(pharmacology)
- Gene Expression Regulation
- Humans
- Interleukin-8
(genetics, metabolism)
- Lipopolysaccharides
(pharmacology)
- Monocytes
(drug effects, metabolism)
- Neutrophils
(drug effects, metabolism)
- Toll-Like Receptor 4
(metabolism)
- Transcription, Genetic
(genetics)
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