Endocrinology, Vol 131, 1037-1046, Copyright © 1992 by Endocrine Society

ARTICLES

Secretion and hormonal regulation of interleukin-6 production by mouse uterine stromal and polarized epithelial cells cultured in vitro

AL Jacobs, PB Sehgal, J Julian and DD Carson
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

Uterine stromal (USC) and uterine epithelial (UEC) cells were isolated from immature and mature mice to determine their ability to secrete interleukin-6 (IL-6) in response to ovarian steroids, IL-1 alpha, and soluble products produced by the heterologous cell type. In addition, the effect of IL-6 on embryo attachment and outgrowth in vitro was determined. UEC cultured on nitrocellulose filter inserts in a polarized manner secreted IL-6 with a 2.5- to 5-fold apical vs. basal preference, as determined by a B9 hybridoma cell proliferation assay and enzyme-linked immunosorbent assay. The hormonal status of animals at the time uteri were removed did not influence subsequent secretion of IL-6, as UEC isolated from immature, diestrous, and estrous stage mice exhibited both a similar amount and had a similar apical preference for secretion of IL-6. The addition of 17 beta-estradiol (E) to UEC cultures markedly inhibited total IL-6 secretion, but did not affect vectorial secretion. The inhibitory effect of E on IL-6 secretion by UEC was consistent with an apparent decrease in IL-6 transcript observed by a reverse transcriptase polymerase chain reaction assay. Other transcripts detected by this assay in UEC included IL-1 alpha, but not IL-1 beta or tumor necrosis factor-alpha. Secretion of IL-6 by UEC was not stimulated by IL-1 alpha, conditioned medium from USC, or coculture with USC. USC secreted IL-6, and while this also was inhibited by E, progesterone was more effective in this regard at physiological concentrations. In addition, there was a synergistic effect of E plus progesterone on inhibition of IL-6 secretion by USC. Secretion of IL-6 by USC was stimulated by IL-1 alpha, and coculture studies demonstrated the ability of UEC to stimulate a several-fold increase in IL-6 secretion by USC. The cytokine transcripts detected in USC cultures included IL-6 and IL-1 alpha, but not IL-1 beta. Transcripts for tumor necrosis factor-alpha were present in USC only after culture with IL-1 alpha. IL-6 added to blastocysts on laminin-coated tissue culture wells resulted in a transient inhibition of the rate of blastocyst attachment and, to a greater extent, an inhibition of the rate of embryo outgrowth. In addition, IL-6 inhibited the size of embryo outgrowths at 24 and 48 h of culture.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				E. M MacDonald, A. Savoy, A. Gillgrass, S. Fernandez, M. Smieja, K. L Rosenthal, A. A Ashkar, and C. Kaushic Susceptibility of Human Female Primary Genital Epithelial Cells to Herpes Simplex Virus, Type-2 and the Effect of TLR3 Ligand and Sex Hormones on Infection Biol Reprod, December 1, 2007; 77(6): 1049 - 1059. [Abstract] [Full Text] [PDF]

				G. Soboll, L. Shen, and C. R. Wira Expression of Toll-Like Receptors (TLR) and Responsiveness to TLR Agonists by Polarized Mouse Uterine Epithelial Cells in Culture Biol Reprod, July 1, 2006; 75(1): 131 - 139. [Abstract] [Full Text] [PDF]

				F. Modugno, R. B. Ness, C. Chen, and N. S. Weiss Inflammation and Endometrial Cancer: A Hypothesis Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2840 - 2847. [Abstract] [Full Text] [PDF]

				M. A. Crane-Godreau and C. R. Wira Effects of Estradiol on Lipopolysaccharide and Pam3Cys Stimulation of CCL20/Macrophage Inflammatory Protein 3 Alpha and Tumor Necrosis Factor Alpha Production by Uterine Epithelial Cells in Culture Infect. Immun., July 1, 2005; 73(7): 4231 - 4237. [Abstract] [Full Text] [PDF]

				M. Bhanoori, K. A. Babu, M. Deenadayal, S. Kennedy, and S. Shivaji The Interleukin-6 -174G/C Promoter Polymorphism Is Not Associated With Endometriosis in South Indian Women Reproductive Sciences, July 1, 2005; 12(5): 365 - 369. [Abstract] [PDF]

				S. Yoshida, T. Harada, T. Iwabe, F. Taniguchi, M. Mitsunari, N. Yamauchi, I. Deura, S. Horie, and N. Terakawa A combination of interleukin-6 and its soluble receptor impairs sperm motility: implications in infertility associated with endometriosis Hum. Reprod., August 1, 2004; 19(8): 1821 - 1825. [Abstract] [Full Text] [PDF]

				K. S. Grant and C. R. Wira Effect of Mouse Uterine Stromal Cells on Epithelial Cell Transepithelial Resistance (TER) and TNF{alpha} and TGF{beta} Release in Culture Biol Reprod, September 1, 2003; 69(3): 1091 - 1098. [Abstract] [Full Text] [PDF]

				C. R. Wira, M. A. Roche, and R. M. Rossoll Antigen Presentation by Vaginal Cells: Role of TGF{beta} as a Mediator of Estradiol Inhibition of Antigen Presentation Endocrinology, August 1, 2002; 143(8): 2872 - 2879. [Abstract] [Full Text] [PDF]

				M.A. Bedaiwy, T. Falcone, R.K. Sharma, J.M. Goldberg, M. Attaran, D.R. Nelson, and A. Agarwal Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial Hum. Reprod., February 1, 2002; 17(2): 426 - 431. [Abstract] [Full Text] [PDF]

				A. J. Levi, J. H. Segars, B. T. Miller, and M. P. Leondires Endometrial cavity fluid is associated with poor ovarian response and increased cancellation rates in ART cycles Hum. Reprod., December 1, 2001; 16(12): 2610 - 2615. [Abstract] [Full Text] [PDF]

				C. de Vantery Arrighi, H. Lucas, D. El-Mowafi, A. Campana, and D. Chardonnens Effects of human hydrosalpinx fluid on in-vitro murine fertilization Hum. Reprod., April 1, 2001; 16(4): 676 - 682. [Abstract] [Full Text] [PDF]

				S. Deb, C. Tessier, A. Prigent-Tessier, U. Barkai, S. Ferguson-Gottschall, R. K. Srivastava, J. Faliszek, and G. Gibori The Expression of Interleukin-6 (IL-6), IL-6 Receptor, and gp130-Kilodalton Glycoprotein in the Rat Decidua and a Decidual Cell Line: Regulation by 17{beta}-Estradiol and Prolactin Endocrinology, October 1, 1999; 140(10): 4442 - 4450. [Abstract] [Full Text]

				R. J. Roper, J. S. Griffith, C. R. Lyttle, R. W. Doerge, A. W. McNabb, R. E. Broadbent, and C. Teuscher Interacting Quantitative Trait Loci Control Phenotypic Variation in Murine Estradiol-Regulated Responses Endocrinology, February 1, 1999; 140(2): 556 - 561. [Abstract] [Full Text]

				D. L. Buchanan, T. Kurita, J. A. Taylor, D. B. Lubahn, G. R. Cunha, and P. S. Cooke Role of Stromal and Epithelial Estrogen Receptors in Vaginal Epithelial Proliferation, Stratification, and Cornification Endocrinology, October 1, 1998; 139(10): 4345 - 4352. [Abstract] [Full Text] [PDF]

				J Julian, R Chiquet-Ehrismann, H. Erickson, and D. Carson Tenascin is induced at implantation sites in the mouse uterus and interferes with epithelial cell adhesion Development, January 3, 1994; 120(3): 661 - 671. [Abstract] [PDF]