PMID- 27849015
OWN - NLM
STAT- MEDLINE
DCOM- 20180516
LR  - 20181202
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Nov 16
TI  - Sterile inflammation as a factor in human male infertility: Involvement of Toll 
      like receptor 2, biglycan and peritubular cells.
PG  - 37128
LID - 10.1038/srep37128 [doi]
LID - 37128
AB  - 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.
FAU - Mayer, C
AU  - Mayer C
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
FAU - Adam, M
AU  - Adam M
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
AD  - Turku Center for Disease Modeling and Department of Physiology, Institute of 
      Biomedicine, University of Turku, FL-20520 Turku, Finland.
FAU - Glashauser, L
AU  - Glashauser L
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
FAU - Dietrich, K
AU  - Dietrich K
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
FAU - Schwarzer, J U
AU  - Schwarzer JU
AD  - Andrology-Center, D-81241 Munich, Germany.
FAU - Kohn, F-M
AU  - Kohn FM
AD  - Andrologicum, D-80331 Munich, Germany.
FAU - Strauss, L
AU  - Strauss L
AD  - Turku Center for Disease Modeling and Department of Physiology, Institute of 
      Biomedicine, University of Turku, FL-20520 Turku, Finland.
FAU - Welter, H
AU  - Welter H
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
FAU - Poutanen, M
AU  - Poutanen M
AD  - Turku Center for Disease Modeling and Department of Physiology, Institute of 
      Biomedicine, University of Turku, FL-20520 Turku, Finland.
FAU - Mayerhofer, A
AU  - Mayerhofer A
AD  - Biomedical Center (BMC), Cell Biology, Anatomy III, 
      Ludwig-Maximilians-Universitat (LMU), D-82152 Planegg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161116
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biglycan)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Serum Amyloid P-Component)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 148591-49-5 (PTX3 protein)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adult
MH  - Biglycan/*metabolism/pharmacology
MH  - C-Reactive Protein/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Estradiol/analogs & derivatives/biosynthesis/pharmacology
MH  - Fulvestrant
MH  - Humans
MH  - Infertility, Male/*metabolism/pathology
MH  - Inflammation/metabolism/pathology
MH  - Interleukin-6/metabolism
MH  - Male
MH  - Middle Aged
MH  - Seminiferous Tubules/*metabolism/pathology
MH  - Serum Amyloid P-Component/metabolism
MH  - Toll-Like Receptor 2/*metabolism
PMC - PMC5111051
EDAT- 2016/11/17 06:00
MHDA- 2018/05/17 06:00
PMCR- 2016/11/16
CRDT- 2016/11/17 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2016/10/25 00:00 [accepted]
PHST- 2016/11/17 06:00 [entrez]
PHST- 2016/11/17 06:00 [pubmed]
PHST- 2018/05/17 06:00 [medline]
PHST- 2016/11/16 00:00 [pmc-release]
AID - srep37128 [pii]
AID - 10.1038/srep37128 [doi]
PST - epublish
SO  - Sci Rep. 2016 Nov 16;6:37128. doi: 10.1038/srep37128.