Antiviral responses of human Fallopian tube epithelial cells to toll-like receptor 3 agonist poly(I:C).
OBJECTIVE
To examine the expression of toll-like receptors (TLR) by primary human Fallopian tube epithelial cells (FTEC) and to determine whether exposure to the TLR3 agonist poly(I:C) induces an antiviral response.


METHODS
Tissue culture study.


METHODS
University medical center.


METHODS
Premenopausal women undergoing hysterectomy.


METHODS
Primary human FTEC were grown to confluence and high transepithelial resistance and treated with TLR agonists. Conditioned media was collected and RNA was extracted and analyzed for the expression of cytokines, chemokines, and antimicrobial genes.


METHODS
The RNA was analyzed by real-time polymerase chain reaction and protein levels were assessed by enzyme-linked immunosorbent assay.


RESULTS
The FTEC were demonstrated to express TLR1-9 but not 10. Treatment of FTEC with TLR3 agonist poly(I:C) resulted in increased expression of interleukin-8, tumor-necrosis factor alpha, human beta-defensin 2, interferon beta, and interferon stimulated genes myxovirus resistance gene 1, 2',5'-oligoadenylate synthetase, and protein kinase R. Additionally, FTEC exposed to poly(I:C) also resulted in the induction of TLR2, TLR3, and TLR7.


CONCLUSIONS
Our results suggest that FTEC are sensitive to viral infection and/or exposure to viral double-stranded RNA and can respond by secreting proinflammatory cytokines that mediate the initiation of an inflammatory response as well as expressing genes that can directly inhibit viral replication.
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. mimi.ghosh@dartmouth.edu
Mimi
M
Ghosh
Todd M
TM
Schaefer
John V
JV
Fahey
Jacqueline A
JA
Wright
Charles R
CR
Wira
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005187:Fallopian Tubes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D064547:Myxovirus Resistance Proteins; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014780:Viruses / Q000276:immunology*; D015054:Zymosan / Q000494:pharmacology; D023083:beta-Defensins / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
C106641:DEFB4A protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D015054:Zymosan; D019892:eIF-2 Kinase; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins; D011070:Poly I-C