Affiliation:
1. Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001
Abstract
ABSTRACT
We have previously demonstrated that rat uterine epithelial cells (UEC) produce CCL20/macrophage inflammatory protein 3 alpha (MIP3α) and tumor necrosis factor alpha (TNF-α) in response to live and heat-killed
Escherichia coli
and to the pathogen-associated molecular patterns (PAMP) lipopolysaccharide (LPS) and Pam
3
Cys. To determine whether estradiol (E
2
) modulates PAMP-induced CCL20/MIP3α and TNF-α secretion, primary cultures of rat UEC were incubated with E
2
for 24 h and then treated with LPS or Pam
3
Cys or not treated for an additional 12 h. E
2
inhibited the constitutive secretion of TNF-α and CCL20/MIP3α into culture media. Interestingly, E
2
pretreatment enhanced CCL20/MIP3α secretion due to LPS and Pam
3
Cys administration. In contrast, and at the same time, E
2
lowered the TNF-α response to both PAMP. To determine whether estrogen receptors (ER) mediated the effects of E
2
, epithelial cells were incubated with E
2
and/or ICI 182,780, a known ER antagonist. ICI 182,780 had no effect on E
2
inhibition of constitutive TNF-α and CCL20/MIP3α secretion. In contrast, ICI 182,780 reversed the stimulatory effect of E
2
on LPS- and/or Pam
3
Cys-induced CCL20/MIP3α secretion as well as partially reversed the inhibitory effect of E
2
on TNF-α production by epithelial cells. Overall, these results indicate that E
2
regulates the production of TNF-α and CCL20/MIP3α by UEC in the absence as well as presence of PAMP. Since CCL20/MIP3α has antimicrobial activity and is chemotactic for immune cells, these studies suggest that regulation of CCL20/MIP3α and TNF-α by E
2
and PAMP may have profound effects on innate and adaptive immune responses to microbial challenge in the female reproductive tract.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
26 articles.
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