Open AccessInfluence of thiopental on MAPK and NF-κB activation in A549 cells
Author(s) -
Ruth E. Bundy,
Boglárka Falusi,
Nándor Marczin
Publication year - 2010
Publication title -
interventional medicine and applied science/interventional medicine and applied science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.195
H-Index - 14
eISSN - 2061-5094
pISSN - 2061-1617
DOI - 10.1556/imas.2.2010.1.6
Subject(s) - p38 mitogen activated protein kinases , mapk/erk pathway , blot , tumor necrosis factor alpha , western blot , phosphorylation , medicine , signal transduction , nf κb , inflammation , pharmacology , endocrinology , microbiology and biotechnology , chemistry , biology , biochemistry , gene
Thiopental (TP) along with being an intravenous anaesthetic is frequently used in high doses to treat increased intracranial hypertension. Long-term treatments result in its accumulation in the lungs and an increased incidence of nosocomial infections. Since TP has been shown to modulate TNF-induced inflammatory pathways in lymphocytes, we hypothesised that TP may modulate pro-inflammatory events in human pulmonary epithelial cells. We investigated the potential influence of TP on MAPK and NF- κ B signal transduction pathways in the absence and presence of TNF. TP at 1 mg/ml concentrations produced a 10-fold increase in p38 activation as assessed by Western blotting using monoclonal antibodies specific for double phosphorylated, thereby activated form of p38. This increase in p38 MAPK phosphorylation was evident as early as 10 minutes (4.5-fold), peaked at 60 minutes (11.3-fold) with return towards baseline (3.6-fold) in 2 hours. This response was specific for p38, since there was no evidence for activation of NF- κ B pathway by TP as judged from Western blot analysis of steady-state I κ B levels. TNF activated both p38 (2.4–11.4-fold increases) and depleted I κ B (64–35% of control) in a concentration dependent manner (0.1–10 ng/ml). Interestingly, in the presence of TP, TNF did not produce a further increase in p38 activation. In addition, TP tended to attenuate TNF-induced NF- κ B activation. These data suggest that high dose TP has the capacity to specifically alter p38MAPK activation and to modulate TNF signalling in epithelial cells, which might have implications to immunological responses in the lung.