Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus.
Prostaglandins have a central role in many endocrine functions in mammals, including regulation of the life span of the corpus luteum by prostaglandin F(2alpha) (PGF) and prostaglandin E2 (PGE), which are secreted by the uterine endometrium. However, the uterus is readily infected with bacteria such as Escherichia coli, which disrupt luteolysis. Immune cells detect E. coli by Toll-like receptor 4 (TLR4) binding its pathogenic ligand, lipopolysaccharide (LPS), although signaling requires accessory molecules such as CD14. The objective of this study was to determine the effect of E. coli or LPS on the function of bovine endometrial cells, and whether purified populations of epithelial and stromal cells express the molecules involved in LPS recognition. In addition, because the female sex hormones estradiol and progesterone modify the risk of uterine infection, their effect on the LPS response was investigated. Endometrial explants produced prostaglandins in response to LPS, with an increased ratio of PGE to PGF. Addition of LPS or E. coli to stromal and epithelial cells stimulated production of PGE and PGF and increased their cyclooxygenase 2 mRNA expression. The production of prostaglandins was abrogated by an LPS antagonist. In addition, estradiol and progesterone inhibited the production of PGE and PGF in response to LPS, indicating a role for steroid hormones in the response to bacterial infection. For the first time, Toll-like receptor 4 mRNA and CD14 mRNA and protein were detected in bovine endometrial stromal and epithelial cells by RT-PCR and flow cytometry. In conclusion, epithelial and stromal cells detect and respond to bacteria, which modulate their endocrine function.
Herath
Shan
S
Royal Veterinary College, Department of Veterinary Clinical Sciences, University of London, North Mymms, Hatfield, Hertfordshire AL9 7TA, United Kingdom.
Fischer
Deborah P
DP
Werling
Dirk
D
Williams
Erin J
EJ
Lilly
Sonia T
ST
Dobson
Hilary
H
Bryant
Clare E
CE
Sheldon
I Martin
IM
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D018929:Cell Culture Techniques; D017931:DNA Primers; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011112:Polymyxin B / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism*; D014599:Uterus / Q000502:physiology
D017931:DNA Primers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011453:Prostaglandins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D011112:Polymyxin B