TGF-β Mediates Proinflammatory Seminal Fluid Signaling in Human Cervical Epithelial Cells
Open Access
- 15 July 2012
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 189 (2), 1024-1035
- https://doi.org/10.4049/jimmunol.1200005
Abstract
The cervix is central to the female genital tract immune response to pathogens and foreign male Ags introduced at coitus. Seminal fluid profoundly influences cervical immune function, inducing proinflammatory cytokine synthesis and leukocyte recruitment. In this study, human Ect1 cervical epithelial cells and primary cervical cells were used to investigate agents in human seminal plasma that induce a proinflammatory response. TGF-β1, TGF-β2, and TGF-β3 are abundant in seminal plasma, and Affymetrix microarray revealed that TGF-β3 elicits changes in Ect1 cell expression of several proinflammatory cytokine and chemokine genes, replicating principal aspects of the Ect1 response to seminal plasma. The differentially expressed genes included several induced in the physiological response of the cervix to seminal fluid in vivo. Notably, all three TGF-β isoforms showed comparable ability to induce Ect1 cell expression of mRNA and protein for GM-CSF and IL-6, and TGF-β induced a similar IL-6 and GM-CSF response in primary cervical epithelial cells. TGF-β neutralizing Abs, receptor antagonists, and signaling inhibitors ablated seminal plasma induction of GM-CSF and IL-6, but did not alter IL-8, CCL2 (MCP-1), CCL20 (MIP-3α), or IL-1α production. Several other cytokines present in seminal plasma did not elicit Ect1 cell responses. These data identify all three TGF-β isoforms as key agents in seminal plasma that signal induction of proinflammatory cytokine synthesis in cervical cells. Our findings suggest that TGF-β in the male partner’s seminal fluid may influence cervical immune function after coitus in women, and potentially be a determinant of fertility, as well as defense from infection.This publication has 74 references indexed in Scilit:
- Seminal Plasma Enhances Cervical Adenocarcinoma Cell Proliferation and Tumour Growth In VivoPLOS ONE, 2012
- KEGG for integration and interpretation of large-scale molecular data setsNucleic Acids Research, 2011
- Potential role of multiple members of the kallikrein-related peptidase family of serine proteases in activating latent TGFβ1 in semenBiological Chemistry, 2010
- Seminal Fluid Drives Expansion of the CD4+CD25+ T Regulatory Cell Pool and Induces Tolerance to Paternal Alloantigens in Mice1Biology of Reproduction, 2009
- Female Infertility and Disrupted Angiogenesis Are Actions of Specific Follistatin IsoformsMolecular Endocrinology, 2008
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002
- Transforming growth factor-β in T-cell biologyNature Reviews Immunology, 2002
- Fertility Impairment in Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice1Biology of Reproduction, 1999
- Plasmin, Substilisin-like Endoproteases, Tissue Plasminogen Activator, and Urokinase Plasminogen Activator Are Involved in Activation of Latent TGF-β1in Human Seminal PlasmaBiochemical and Biophysical Research Communications, 1998
- The Leukocytic Reaction of the Human Uterine CervixAmerican Journal of Reproductive Immunology, 1992