Activation of transcription factors in a mouse lung following exposure to environmental chemical and biological agents.
Environmental biological and chemical agents can modulate innate and acquired immunity in the lung via the stimulation of Toll-like receptors (TLRs). To investigate the effect of environmental chemical agents on the activation of NF-κB and activator protein (AP)-1 subunits and the role of TLR4 signaling in the lung, C3H/HeN and C3H/HeJ (TLR4-defective) mice were exposed to 0 or 50 ppm of toluene for 6 hr/day, 5 days/week for 6 weeks. Some groups of mice were also stimulated with OVA or LPS as a biological agent. The DNA-binding activities of the NF-κB subunits (p50, p52, p65 and RelB) and AP-1 family members (FosB, c-Fos, +c-Jun, JunD) were compared using TransAM ELISA kits. Exposure to toluene alone produced no significant changes in both mice. Although stimulation with OVA or LPS alone significantly increased the DNA binding activities of p50 and p52 in C3H/HeN mice, there were no interactions between biological factors and toluene. In the C3H/HeJ mice, stimulation with OVA or LPS increased p65 and p52 binding activity and the combination of exposure to toluene and OVA significantly increased the DNA binding activities of the p65 and p52 in the lung. During AP-1 activation, co-exposure to toluene and OVA increased JunD binding activity in C3H/HeJ mice, while co-exposure to toluene and LPS influenced c-Fos binding activity in C3H/HeN mice. These results indicate that TLR4 may play an important role in activation of NF-κB or AP-1 family following exposure to environmental biological and chemical agents.
National Institute for Environmental Studies.
Tin-Tin
TT
Win-Shwe
Hidekazu
H
Fujimaki
D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D004247:DNA / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000009:adverse effects*; D011485:Protein Binding; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014050:Toluene / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000393:Air Pollutants; D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D014050:Toluene; D010047:Ovalbumin; D004247:DNA