PMID- 21377791
OWN - NLM
STAT- MEDLINE
DCOM- 20110808
LR  - 20131121
IS  - 1873-3336 (Electronic)
IS  - 0304-3894 (Linking)
VI  - 189
IP  - 1-2
DP  - 2011 May 15
TI  - Ubiquitous hazardous metal lead induces TNF-alpha in human phagocytic THP-1 cells: 
      primary role of ERK 1/2.
PG  - 255-64
LID - 10.1016/j.jhazmat.2011.02.027 [doi]
AB  - Induction of tumor necrosis factor-alpha (TNF-alpha) in response to lead (Pb) exposure 
      has been implicated in its immunotoxicity. However, the molecular mechanism by 
      which Pb upregulates the level of TNF-alpha is wagely known. An attempt was therefore 
      made to elucidate the mechanistic aspect of TNF-alpha induction, mainly focusing 
      transcriptional and post transcriptional regulation via mitogen activated protein 
      kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic 
      THP-1 cells resulted in significant enhanced production of TNF-alpha m-RNA and 
      protein secretion. Moreover, the stability of TNF-alpha m-RNA was also increased as 
      indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb 
      exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused 
      significant inhibition in production and stability of TNF-alpha m-RNA. However, SB 
      203580 partially inhibited production and stability of TNF-alpha m-RNA. 
      Interestingly, a combined exposure of these two inhibitors completely blocked 
      modulation of TNF-alpha m-RNA. Data tends to suggest that expression and stability of 
      TNF-alpha induction due to Pb exposure is mainly regulated through ERK. Briefly, 
      these observations are useful in understanding some mechanistic aspects of 
      proinflammatory and immunotoxicity of Pb, a globally acknowledged key 
      environmental contaminant.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Khan, Mohd Imran
AU  - Khan MI
AD  - Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of 
      Scientific & Industrial Research, Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, 
      UP, India.
FAU - Islam, Najmul
AU  - Islam N
FAU - Sahasrabuddhe, Amogh A
AU  - Sahasrabuddhe AA
FAU - Mahdi, Abbas Ali
AU  - Mahdi AA
FAU - Siddiqui, Huma
AU  - Siddiqui H
FAU - Ashquin, Mohd
AU  - Ashquin M
FAU - Ahmad, Iqbal
AU  - Ahmad I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110217
PL  - Netherlands
TA  - J Hazard Mater
JT  - Journal of hazardous materials
JID - 9422688
RN  - 0 (Hazardous Substances)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2P299V784P (Lead)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Cell Line
MH  - Hazardous Substances/immunology/*pharmacology
MH  - Humans
MH  - Lead/immunology/*pharmacology
MH  - Mitogen-Activated Protein Kinase 3/physiology
MH  - Phagocytes/drug effects/*metabolism
MH  - RNA Stability
MH  - RNA, Messenger
MH  - Transcriptional Activation/*drug effects
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2011/03/08 06:00
MHDA- 2011/08/09 06:00
CRDT- 2011/03/08 06:00
PHST- 2010/09/03 00:00 [received]
PHST- 2011/02/11 00:00 [revised]
PHST- 2011/02/11 00:00 [accepted]
PHST- 2011/03/08 06:00 [entrez]
PHST- 2011/03/08 06:00 [pubmed]
PHST- 2011/08/09 06:00 [medline]
AID - S0304-3894(11)00228-7 [pii]
AID - 10.1016/j.jhazmat.2011.02.027 [doi]
PST - ppublish
SO  - J Hazard Mater. 2011 May 15;189(1-2):255-64. doi: 10.1016/j.jhazmat.2011.02.027. 
      Epub 2011 Feb 17.