Inorganic mercury exposure in prairie voles (Microtus ochrogaster) alters the expression of toll-like receptor 4 and activates inflammatory pathways in the liver in a sex-specific manner

S. Assefa, Tom Curtis, S. Sethi, Randall Davis, Y. Chen, Rashmi Kaul

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.

Original languageEnglish
Pages (from-to)376-386
Number of pages11
JournalHuman and Experimental Toxicology
Volume31
Issue number4
DOIs
StatePublished - 1 Apr 2012

Fingerprint

Arvicolinae
Toll-Like Receptor 4
Mercury
Liver
p38 Mitogen-Activated Protein Kinases
Cell signaling
Grassland
Toll-Like Receptor 2
Proto-Oncogene Proteins c-akt
Detoxification
Immunomodulation
NF-kappa B
Environmental Exposure
Biomarkers
Drinking Water
Contamination

Keywords

  • NF-κB
  • TLR
  • biomarker
  • inflammation
  • mercury
  • p38 MAPK
  • prairie vole

Cite this

@article{5f0a6f5ad2d14098b049aeab46612dd4,
title = "Inorganic mercury exposure in prairie voles (Microtus ochrogaster) alters the expression of toll-like receptor 4 and activates inflammatory pathways in the liver in a sex-specific manner",
abstract = "Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.",
keywords = "NF-κB, TLR, biomarker, inflammation, mercury, p38 MAPK, prairie vole",
author = "S. Assefa and Tom Curtis and S. Sethi and Randall Davis and Y. Chen and Rashmi Kaul",
year = "2012",
month = "4",
day = "1",
doi = "10.1177/0960327111407223",
language = "English",
volume = "31",
pages = "376--386",
journal = "Human and Experimental Toxicology",
issn = "0960-3271",
publisher = "SAGE Publications Inc.",
number = "4",

}

TY - JOUR

T1 - Inorganic mercury exposure in prairie voles (Microtus ochrogaster) alters the expression of toll-like receptor 4 and activates inflammatory pathways in the liver in a sex-specific manner

AU - Assefa, S.

AU - Curtis, Tom

AU - Sethi, S.

AU - Davis, Randall

AU - Chen, Y.

AU - Kaul, Rashmi

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.

AB - Environmental exposure to mercury can cause a number of adverse effects in humans including the disruption of endocrine function that may result in sex-specific effects. The present study was designed to characterize sex-specific effects of chronic inorganic mercury exposure on toll-like receptor (TLR) 2 and TLR4 and inflammatory signaling in the liver of prairie voles (Microtus ochrogaster). Following 10 weeks of exposure to mercury via drinking water, effects on protein expression levels of TLR2 and TLR4 and the downstream p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa (NF-κB) signaling pathways were assessed. Using immunoblot analysis, we found that mercury exposure significantly enhanced the expression of TLR4 and activated p38 MAPK and NF-κB pathways in vole livers. This is the first report indicating that TLR4 may serve as a sensor for chronic mercury exposure in the liver. Further, compared to females, mercury-treated male voles exhibited significant increases in activated p38 MAPK and a greater extent of liver damage. Together, these findings establish sex-specific liver immunomodulation and cellular signaling following chronic inorganic mercury exposure. Furthermore, this study also supports the use of voles as biomarkers of environmental mercury contamination and offers a promising in vivo tool to test various therapeutic strategies for mercury detoxification.

KW - NF-κB

KW - TLR

KW - biomarker

KW - inflammation

KW - mercury

KW - p38 MAPK

KW - prairie vole

UR - http://www.scopus.com/inward/record.url?scp=84860495397&partnerID=8YFLogxK

U2 - 10.1177/0960327111407223

DO - 10.1177/0960327111407223

M3 - Article

C2 - 21558144

AN - SCOPUS:84860495397

VL - 31

SP - 376

EP - 386

JO - Human and Experimental Toxicology

JF - Human and Experimental Toxicology

SN - 0960-3271

IS - 4

ER -