PMID- 18675330
OWN - NLM
STAT- MEDLINE
DCOM- 20081125
LR  - 20131121
IS  - 0378-4274 (Print)
IS  - 0378-4274 (Linking)
VI  - 181
IP  - 2
DP  - 2008 Sep 26
TI  - Activation of MAPK/AP-1 signaling pathway in lung injury induced by 2-chloroethyl 
      ethyl sulfide, a mustard gas analog.
PG  - 112-7
LID - 10.1016/j.toxlet.2008.07.005 [doi]
AB  - We reported earlier that the activation of free-radical-mediated tumor necrosis 
      factor-alpha (TNF-alpha) cascade is the major pathway in the inflammatory lung 
      disease induced by 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog. 
      TNF-alpha induces activating protein 1 (AP-1) activation via phosphorylation of 
      mitogen activated protein kinases (MAPKs). The present study examines the 
      relationship between CEES induced lung injury and MAPKs signaling pathway. Adult 
      guinea pigs received single intratracheal injection of different doses of CEES 
      and were sacrificed at different time points. CEES exposure caused lung injury 
      with evidence of fibrosis. The optimum activation of all members of the MAPKs 
      family (ERK1/2, p38 and JNK1/2) was achieved at 0.5 mg/kg dose and at 1h. No 
      significant change was observed beyond that time point. This led to an activation 
      of AP-1 transcription factors associated with an increase in the protein levels 
      of Fos, activating transcription factor (ATF) and Jun family members. To explore 
      the involvement of AP-1 in cell proliferation, we determined the protein levels 
      of cell cycle protein cyclin D1 and cell differentiation marker proliferating 
      cell nuclear antigen (PCNA). An up regulation of these proteins was observed. 
      Hence it is suggested that CEES exposure causes accumulation of TNF-alpha, which 
      is associated with an activation of MAPK/AP-1 signaling pathway and cell 
      proliferation. Further studies are needed to clarify whether the observed effects 
      are the adaptive responses of the lung or they contribute to the lung injury.
FAU - Mukhopadhyay, Sutapa
AU  - Mukhopadhyay S
AD  - Department of Cancer Biology, Meharry Medical College, 1005 David Todd Blvd., 
      Nashville, TN 37208, USA.
FAU - Mukherjee, Shyamali
AU  - Mukherjee S
FAU - Smith, Milton
AU  - Smith M
FAU - Das, Salil K
AU  - Das SK
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080715
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 136601-57-5 (Cyclin D1)
RN  - 693-07-2 (2-chloroethyl ethyl sulfide)
RN  - 9007-49-2 (DNA)
RN  - T8KEC9FH9P (Mustard Gas)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cyclin D1/analysis
MH  - DNA/metabolism
MH  - Guinea Pigs
MH  - Lung/*drug effects
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Mustard Gas/*analogs & derivatives/toxicity
MH  - Proliferating Cell Nuclear Antigen/analysis
MH  - Signal Transduction/*drug effects
MH  - Transcription Factor AP-1/*physiology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2008/08/05 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/08/05 09:00
PHST- 2008/05/07 00:00 [received]
PHST- 2008/07/02 00:00 [revised]
PHST- 2008/07/02 00:00 [accepted]
PHST- 2008/08/05 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/05 09:00 [entrez]
AID - S0378-4274(08)01077-1 [pii]
AID - 10.1016/j.toxlet.2008.07.005 [doi]
PST - ppublish
SO  - Toxicol Lett. 2008 Sep 26;181(2):112-7. doi: 10.1016/j.toxlet.2008.07.005. Epub 
      2008 Jul 15.