Downregulation of cilia-localized Il-6R alpha by 17beta-estradiol in mouse and human fallopian tubes.
The action of interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6R alpha and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6R alpha is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17beta-estradiol (E(2)), but not progesterone (P(4)), causes a time-dependent decrease in IL-6R alpha expression, which is blocked by the estrogen receptor (ER) antagonist ICI-182,780. Exposure of different ER-selective agonists propyl-(1H)-pyrazole-1,3,5-triyl-trisphenol or 2,3-bis-(4-hydroxyphenyl)-propionitrile demonstrated an ER subtype-specific regulation of IL-6R alpha in mouse fallopian tubes. In contrast to IL-6R alpha, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6R alpha and gp130 in IL-6 knockout mice was found to be normal; however, E(2) treatment increased IL-6R alpha, but not gp130, in IL-6 knockout mice when compared with wild-type mice. Furthermore, expression levels of IL-6R alpha, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings open the possibility that cilia-specific IL-6R alpha may play a role in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6R alpha in the fallopian tube.
Dept. of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Univ. of Gothenburg, Medicinareg 11, PO Box 434, Gothenburg 40530, Sweden. ruijin.shao@fysiologi.gu.se
Ruijin
R
Shao
Magdalena
M
Nutu
Linda
L
Karlsson-Lindahl
Anna
A
Benrick
Birgitta
B
Weijdegård
Susanne
S
Lager
Emil
E
Egecioglu
Julia
J
Fernandez-Rodriguez
Kristina
K
Gemzell-Danielsson
Claes
C
Ohlsson
John-Olov
JO
Jansson
Håkan
H
Billig
D000328:Adult; D000818:Animals; D002923:Cilia / Q000378:metabolism; D054885:Cumulus Cells / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005187:Fallopian Tubes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; C508603:IL6R protein, human; C494199:IL6ST protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D011374:Progesterone; D004958:Estradiol