PMID- 22178267
OWN - NLM
STAT- MEDLINE
DCOM- 20120321
LR  - 20240315
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 292
IP  - 2-3
DP  - 2012 Feb 26
TI  - Protein adducts of malondialdehyde and 4-hydroxynonenal contribute to 
      trichloroethene-mediated autoimmunity via activating Th17 cells: dose- and 
      time-response studies in female MRL+/+ mice.
PG  - 113-22
LID - 10.1016/j.tox.2011.12.001 [doi]
AB  - Trichloroethene (TCE), a common occupational and environmental toxicant, is known 
      to induce autoimmunity. Previous studies in our laboratory showed increased 
      oxidative stress in TCE-mediated autoimmunity. To further establish the role of 
      oxidative stress and to investigate the mechanisms of TCE-mediated autoimmunity, 
      dose- and time-response studies were conducted in MRL+/+ mice by treating them 
      with TCE via drinking water at doses of 0.5, 1.0 or 2.0mg/ml for 12, 24 or 36 
      weeks. TCE exposure led to dose-related increases in malondialdehyde 
      (MDA)-/hydroxynonenal (HNE)-protein adducts and their corresponding antibodies in 
      the sera and decreases in GSH and GSH/GSSG ratio in the kidneys at 24 and 36 
      weeks, with greater changes at 36 weeks. The increases in these protein adducts 
      and decreases in GSH/GSSG ratio were associated with significant elevation in 
      serum anti-nuclear- and anti-ssDNA-antibodies, suggesting an association between 
      TCE-induced oxidative stress and autoimmune response. Interestingly, splenocytes 
      from mice treated with TCE for 24 weeks secreted significantly higher levels of 
      IL-17 and IL-21 than did splenocytes from controls after stimulation with 
      MDA-mouse serum albumin (MSA) or HNE-MSA adducts. The increased release of these 
      cytokines showed a dose-related response and was more pronounced in mice treated 
      with TCE for 36 weeks. These studies provide evidence that MDA- and or 
      HNE-protein adducts contribute to TCE-mediated autoimmunity, which may be via 
      activation of Th17 cells.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Wang, Gangduo
AU  - Wang G
AD  - Department of Pathology, University of Texas Medical Branch, Galveston, TX 
      77555-0609, USA.
FAU - Wang, Jianling
AU  - Wang J
FAU - Fan, Xiuzhen
AU  - Fan X
FAU - Ansari, G A S
AU  - Ansari GA
FAU - Khan, M Firoze
AU  - Khan MF
LA  - eng
GR  - R01 ES016302/ES/NIEHS NIH HHS/United States
GR  - R01 ES016302-05/ES/NIEHS NIH HHS/United States
GR  - ES016302/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20111209
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Aldehydes)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukins)
RN  - 0 (Solvents)
RN  - 290YE8AR51 (Trichloroethylene)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - GAN16C9B8O (Glutathione)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Aldehydes/*immunology
MH  - Animals
MH  - Autoimmune Diseases/*chemically induced/immunology
MH  - Autoimmunity/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glutathione/immunology
MH  - Interleukin-17/immunology
MH  - Interleukins/immunology
MH  - Kidney/enzymology
MH  - Malondialdehyde/*immunology
MH  - Mice
MH  - Mice, Inbred MRL lpr
MH  - Solvents
MH  - Statistics, Nonparametric
MH  - Trichloroethylene/*toxicity
PMC - PMC3264691
MID - NIHMS343527
EDAT- 2011/12/20 06:00
MHDA- 2012/03/22 06:00
PMCR- 2013/02/26
CRDT- 2011/12/20 06:00
PHST- 2011/09/22 00:00 [received]
PHST- 2011/11/22 00:00 [revised]
PHST- 2011/12/01 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/03/22 06:00 [medline]
PHST- 2013/02/26 00:00 [pmc-release]
AID - S0300-483X(11)00506-3 [pii]
AID - 10.1016/j.tox.2011.12.001 [doi]
PST - ppublish
SO  - Toxicology. 2012 Feb 26;292(2-3):113-22. doi: 10.1016/j.tox.2011.12.001. Epub 
      2011 Dec 9.