PMID- 23123736
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20181202
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 365
IP  - 2
DP  - 2013 Jan 30
TI  - Damaged spermatogenic cells induce inflammatory gene expression in mouse Sertoli 
      cells through the activation of Toll-like receptors 2 and 4.
PG  - 162-73
LID - S0303-7207(12)00468-6 [pii]
LID - 10.1016/j.mce.2012.10.016 [doi]
AB  - Testicular inflammation, including noninfectious inflammatory responses in the 
      testis, may impair male fertility. Mechanisms underlying the initiation of 
      noninfectious testicular inflammation are poorly understood. In the current 
      study, we demonstrate that damaged spermatogenic cell products (DSCPs) induce 
      expression of various inflammatory mediators, including TNF-alpha, IL-1beta, IL-6, and 
      macrophage chemotactic protein 1 (MCP-1), in Sertoli cells. Notably, the 
      DSCP-induced inflammatory gene expression was significantly reduced by knockout 
      Toll-like receptor (TLR)2 or TLR4, and abolished by double knockout TLR2 and TLR4 
      (TLR2(-/-)TLR4(-/-)). MCP-1 secreted by Sertoli cells after stimulation with 
      DSCPs promotes macrophage migration. We also provide evidence that 
      busulfan-induced spermatogenic cell damages in vivo upregulate TNF-alpha and MCP-1 
      expression in Sertoli cells, and facilitate macrophage infiltration into the 
      testis in wild-type mice. These phenomena were not observed in TLR2(-/-)TLR4(-/-) 
      mice. Data indicate that DSCPs induce inflammatory gene expression in Sertoli 
      cells via the activation of TLR2 and TLR4, which may initiate noninfectious 
      inflammatory responses in the testis. The results provide novel insights into the 
      mechanisms underlying damaged spermatogenic cell-induced testicular inflammation.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Zhang, Xiaoyan
AU  - Zhang X
AD  - Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy 
      of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 
      Beijing, China.
FAU - Wang, Tao
AU  - Wang T
FAU - Deng, Tingting
AU  - Deng T
FAU - Xiong, Weipeng
AU  - Xiong W
FAU - Lui, Peng
AU  - Lui P
FAU - Li, Nan
AU  - Li N
FAU - Chen, Yongmei
AU  - Chen Y
FAU - Han, Daishu
AU  - Han D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121030
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemotaxis
MH  - Culture Media, Conditioned
MH  - Gene Expression
MH  - *Gene Expression Regulation
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-1beta/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - MAP Kinase Signaling System
MH  - Macrophages, Peritoneal/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Necrosis
MH  - Orchitis/metabolism
MH  - Sertoli Cells/immunology/*metabolism
MH  - Spermatogonia/metabolism/pathology/physiology
MH  - Toll-Like Receptor 2/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Up-Regulation
EDAT- 2012/11/06 06:00
MHDA- 2013/06/19 06:00
CRDT- 2012/11/06 06:00
PHST- 2012/04/16 00:00 [received]
PHST- 2012/09/13 00:00 [revised]
PHST- 2012/10/16 00:00 [accepted]
PHST- 2012/11/06 06:00 [entrez]
PHST- 2012/11/06 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - S0303-7207(12)00468-6 [pii]
AID - 10.1016/j.mce.2012.10.016 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2013 Jan 30;365(2):162-73. doi: 10.1016/j.mce.2012.10.016. 
      Epub 2012 Oct 30.