Estradiol attenuates lipopolysaccharide-induced CXC chemokine ligand 8 production by human peripheral blood monocytes.
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.
Pioli
Patricia A
PA
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Jensen
Amy L
AL
Weaver
Lehn K
LK
Amiel
Eyal
E
Shen
Zheng
Z
Shen
Li
L
Wira
Charles R
CR
Guyre
Paul M
PM
D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D016209:Interleukin-8; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004958:Estradiol