Human oviductal epithelial cells express Toll-like receptor 3 and respond to double-stranded RNA: Fallopian tube-specific mucosal immunity against viral infection.
BACKGROUND
The aim of this study was to evaluate the site-specific immunoregulatory mechanisms against viral infection in human Fallopian tubes.


METHODS
We therefore investigated the effects of double-stranded RNA (dsRNA) on the production of interleukin (IL)-6, IL-8 and granulocyte chemotactic protein-2 (GCP-2) by cultured oviductal epithelial cells (OECs) using enzyme-linked immunosorbent assays. Phosphorylation of inhibitor kappaB-alpha (IkappaB-alpha) protein after dsRNA stimulation and the expression of Toll-like receptor (TLR) 3 in these cells were also evaluated by western blot analysis.


RESULTS
Polyriboinosinic:polyribocytidylic acid (poly I:C), a synthetic dsRNA that antagonizes TLR3, stimulated the secretion of IL-6, IL-8 and GCP-2 by OECs. Poly I:C-induced production of these cytokines by OECs was inhibited by the pretreatment of these cells with anti-TLR3 antibody. The phosphorylation of IkappaB-alpha protein was detected in OECs after stimulation by poly I:C. The expression of TLR3 was also detected in OECs.


CONCLUSIONS
These results suggest that the epithelial cells of the human Fallopian tube have evolved a unique, site-specific mechanism for recognizing viral infection. TLR3-mediated production of proinflammatory cytokines and chemokines in OECs in response to viral dsRNA may be important for antiviral immunity in the human female reproductive tract.
Nasu
K
K
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan. nasu@med.oita-u.ac.jp
Itoh
H
H
Yuge
A
A
Nishida
M
M
Narahara
H
H
D000328:Adult; D002478:Cells, Cultured; D054427:Chemokine CXCL6; D019743:Chemokines, CXC / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005187:Fallopian Tubes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018928:Immunity, Mucosal; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha; D011070:Poly I-C / Q000276:immunology; D011089:Polydeoxyribonucleotides / Q000276:immunology; D012330:RNA, Double-Stranded / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis*; D014777:Virus Diseases / Q000276:immunology*
C515503:CXCL6 protein, human; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; C000606204:NFKBIA protein, human; D011089:Polydeoxyribonucleotides; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D000072000:NF-KappaB Inhibitor alpha; C031156:poly d(I-C); D011070:Poly I-C