title: Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells.
abstract: Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man.
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Mayer
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.|Turku Center for Disease Modeling and Department of Physiology, Institute of Biomedicine, University of Turku, FL-20520 Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Glashauser
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dietrich
authors.affiliation: Andrology-Center, D-81241 Munich, Germany.
authors.forename: J U
authors.initials: JU
authors.lastname: Schwarzer
authors.affiliation: Andrologicum, D-80331 Munich, Germany.
authors.forename: F-M
authors.initials: FM
authors.lastname: Köhn
authors.affiliation: Turku Center for Disease Modeling and Department of Physiology, Institute of Biomedicine, University of Turku, FL-20520 Turku, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Strauss
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Welter
authors.affiliation: Turku Center for Disease Modeling and Department of Physiology, Institute of Biomedicine, University of Turku, FL-20520 Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Biomedical Center (BMC), Cell Biology, Anatomy III, Ludwig-Maximilians-Universität (LMU), D-82152 Planegg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mayerhofer
mesh_terms: D000328:Adult; D058578:Biglycan / Q000378:metabolism* / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012671:Seminiferous Tubules / Q000378:metabolism* / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D058578:Biglycan; D002097:C-Reactive Protein; D018932:Chemokine CCL2; D004958:Estradiol; D000077267:Fulvestrant; D015850:Interleukin-6; D000683:Serum Amyloid P-Component; D051195:Toll-Like Receptor 2; D000099153:Pentraxins; C111835:CCL2 protein, human; C508600:IL6 protein, human; C495342:TLR2 protein, human