Migration inhibitory factor secretion by polarized uterine epithelial cells is enhanced in response to the TLR3 agonist poly (I:C).
OBJECTIVE
Uterine epithelial cells produce cytokines that stimulate leukocytes in response to a microbial insult. The goals of this study were to determine if uterine epithelial cells produce the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), and to see if toll-like receptor (TLR) agonists stimulate MIF secretion.


METHODS
Human uterine epithelial cells were isolated and grown in cell culture inserts. Levels of MIF secretion were examined by ELISA and MIF messenger RNA (mRNA) expression was examined using real time RT-PCR.


RESULTS
Uterine epithelial cells constitutively secrete MIF and exposure to the TLR3 agonist poly (I:C) resulted in enhanced apical secretion of MIF. MIF secretion appeared to be from pre-formed intracellular stores, since exposure of epithelial cells to poly (I:C) had little effect on the expression of MIF-mRNA.


CONCLUSIONS
These results demonstrate that uterine epithelial cells constitutively produce MIF and stimulation with poly (I:C) results in enhanced MIF production. This suggests that MIF secretion by uterine epithelial cells may play a critical role in innate immune responses against viral pathogens mediated through TLR3.
Schaefer
Todd M
TM
Department of Physiology, Dartmouth Medical School, 710W Borwell, 1 Medical Center Drive, Lebanon, NH 03756, USA. todd.m.schaefer@dartmouth.edu
Fahey
John V
JV
Wright
Jacqueline A
JA
Wira
Charles R
CR
D000328:Adult; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000502:physiology
D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D011070:Poly I-C