title: Influence of Testosterone on Inflammatory Response in Testicular Cells and Expression of Transcription Factor Foxp3 in T Cells.
abstract: OBJECTIVE
  Previous studies demonstrated a strong association between low androgen levels and reduced capacity to mount an inflammatory response. However, the mechanisms underlying these observations are largely not understood.
  
  
  METHODS
  Generation of CD4+CD25+Foxp3+ regulatory T cells in Leydig cell-conditioned media was determined by flow cytometry and ELISA. Influence of testosterone on cytokine response was measured in LPS-stimulated testicular macrophages, Sertoli and peritubular cells.
  
  
  RESULTS
  Leydig cell-conditioned media dose-dependently stimulated expression of transcription factor Foxp3 and secretion of IL-10 in splenic CD4+ T cells, an effect abolished by addition of the anti-androgen flutamide. In isolated Sertoli and peritubular cells, testosterone pre-treatment suppressed the LPS-induced inflammatory response on TNF-α mRNA expression, while no effect was evident in testicular macrophages (TM).
  
  
  CONCLUSIONS
  Androgens can influence the immune system under normal conditions by the generation and functional differentiation of regulatory T cells and in testicular inflammation by direct effect on Sertoli and peritubular cells.
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Fijak
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Lara-Jil
authors.initials: LJ
authors.lastname: Damm
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Jan-Per
authors.initials: JP
authors.lastname: Wenzel
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Ferial
authors.initials: F
authors.lastname: Aslani
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Walecki
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wahle
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Eisel
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Baal
authors.affiliation: Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Faculty of Veterinary Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Konrad
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Rafiq
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: O'Hara
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
authors.affiliation: Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D007985:Leydig Cells / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013739:Testosterone; D005485:Flutamide
keywords: Foxp3; peritubular cells; sertoli cells; testicular immune response; testicular macrophages; testosterone