Lipopolysaccharide-induced IL-1 beta production by human uterine macrophages up-regulates uterine epithelial cell expression of human beta-defensin 2.
The uterine endometrium coordinates a wide spectrum of physiologic and immunologic functions, including endometrial receptivity and implantation as well as defense against sexually transmitted pathogens. Macrophages and epithelial cells cooperatively mediate innate host defense against bacterial invasion through the generation of immunologic effectors, including cytokines and antimicrobial peptides. In this study, we demonstrate that stimulation of peripheral blood monocytes and uterine macrophages with bacterial LPS induces the production of biologically active proinflammatory IL-1beta. High doses of estradiol enhance LPS-induced IL-1beta expression in an estrogen receptor-dependent manner. Furthermore, both peripheral blood monocyte- and uterine macrophage-derived IL-1beta induce secretion of antimicrobial human beta-defensin 2 by uterine epithelial cells. These data indicate dynamic immunologic interaction between uterine macrophages and epithelial cells and implicate a role for estradiol in the modulation of the immune response.
Pioli
Patricia A
PA
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA. pioli@dartmouth.edu
Weaver
Lehn K
LK
Schaefer
Todd M
TM
Wright
Jacqueline A
JA
Wira
Charles R
CR
Guyre
Paul M
PM
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*; D014599:Uterus / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D023083:beta-Defensins / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; C106641:DEFB4A protein, human; D007375:Interleukin-1; D008070:Lipopolysaccharides; D023083:beta-Defensins; D004958:Estradiol; D020170:Caspase 1