PMID- 28765008
OWN - NLM
STAT- MEDLINE
DCOM- 20171129
LR  - 20201209
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 229
DP  - 2017 Oct
TI  - Microcystin-leucine arginine exhibits immunomodulatory roles in testicular cells 
      resulting in orchitis.
PG  - 964-975
LID - S0269-7491(17)30654-1 [pii]
LID - 10.1016/j.envpol.2017.07.081 [doi]
AB  - Microcystin-leucine arginine (MC-LR) causes testicular inflammation and hinders 
      spermatogenesis. However, the molecular mechanisms underlying the immune 
      responses to MC-LR in the testis have not been elucidated in detail. In this 
      study, we show that MC-LR induced immune responses in Sertoli cells (SC), germ 
      cells (GC), and Leydig cells (LC) via activating phosphatidylinositol 3-kinase 
      (PI3K)/AKT/nuclear factor kappa B (NF-kappaB), resulting in the production of 
      pro-inflammatory cytokines and chemokines including tumor necrosis factor alpha 
      (TNF-alpha), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and 
      chemokine (C-X-C motif) ligand 10 (CXCL10). The observed effects were attributed 
      to reduced activity of protein phosphatases 2A (PP2A) as a result of binding of 
      MC-LR to the catalytic subunit of PP2A in SC and GC. By contrast, innate immune 
      responses were triggered by Toll-like receptor 2 (TLR2) in LC because MC-LR could 
      not enter into the LC and subsequently inhibit the PP2A activity. PI3K/AKT/NF-kappaB 
      were also activated in SC, GC, and LC in vivo, with the enrichment of TNF-alpha, 
      IL-6, MCP-1, and CXCL10 in the testis. Following chronic exposure, MC-LR-treated 
      mice exhibited decreased sperm counts and abnormal sperm morphology. Our data 
      demonstrate that MC-LR can activate innate immune responses in testicular cells, 
      which provides novel insights to explore the mechanism associated with 
      MC-LR-induced orchitis.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Chen, Yabing
AU  - Chen Y
AD  - Immunology and Reproduction Biology Laboratory, State Key Laboratory of 
      Analytical Chemistry for Life Science, Medical School, Nanjing University, 
      Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 
      University, Nanjing 210093, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Immunology and Reproduction Biology Laboratory, State Key Laboratory of 
      Analytical Chemistry for Life Science, Medical School, Nanjing University, 
      Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 
      University, Nanjing 210093, China.
FAU - Zhang, Qin
AU  - Zhang Q
AD  - Immunology and Reproduction Biology Laboratory, State Key Laboratory of 
      Analytical Chemistry for Life Science, Medical School, Nanjing University, 
      Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 
      University, Nanjing 210093, China.
FAU - Xiang, Zou
AU  - Xiang Z
AD  - Department of Health Technology and Informatics, Faculty of Health and Social 
      Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 
      China.
FAU - Li, Dongmei
AU  - Li D
AD  - Immunology and Reproduction Biology Laboratory, State Key Laboratory of 
      Analytical Chemistry for Life Science, Medical School, Nanjing University, 
      Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 
      University, Nanjing 210093, China.
FAU - Han, Xiaodong
AU  - Han X
AD  - Immunology and Reproduction Biology Laboratory, State Key Laboratory of 
      Analytical Chemistry for Life Science, Medical School, Nanjing University, 
      Nanjing 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing 
      University, Nanjing 210093, China. Electronic address: hanxd@nju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170729
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Marine Toxins)
RN  - 0 (Microcystins)
RN  - 0 (TLR2 protein, human)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EQ8332842Y (cyanoginosin LR)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Arginine
MH  - Cell Count
MH  - Chemokine CCL2
MH  - Humans
MH  - Interleukin-6
MH  - Leucine
MH  - Male
MH  - Marine Toxins
MH  - Mice
MH  - Microcystins/*toxicity
MH  - Orchitis/*chemically induced/immunology
MH  - Phosphatidylinositol 3-Kinases
MH  - Protein Phosphatase 2
MH  - Sertoli Cells/*drug effects/immunology
MH  - Spermatogenesis
MH  - Toll-Like Receptor 2
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Immune responses
OT  - Microcystin-LR
OT  - Orchitis
OT  - Testicular cells
EDAT- 2017/08/03 06:00
MHDA- 2017/12/01 06:00
CRDT- 2017/08/03 06:00
PHST- 2017/02/17 00:00 [received]
PHST- 2017/06/06 00:00 [revised]
PHST- 2017/07/24 00:00 [accepted]
PHST- 2017/08/03 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
PHST- 2017/08/03 06:00 [entrez]
AID - S0269-7491(17)30654-1 [pii]
AID - 10.1016/j.envpol.2017.07.081 [doi]
PST - ppublish
SO  - Environ Pollut. 2017 Oct;229:964-975. doi: 10.1016/j.envpol.2017.07.081. Epub 
      2017 Jul 29.