Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

Jinming Zhao, Richart W Harper, Aaron Barchowsky, Y. P Peter Di

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number2
DOIs
StatePublished - Aug 2007

Fingerprint

Smoke
Tobacco
Transcription Factors
Epithelial Cells
Gene Expression
Transcriptional Activation
Protein Array Analysis
DNA
Environmental Exposure
Oligonucleotide Array Sequence Analysis
Complex Mixtures
Fluorescence Microscopy
Western Blotting
Phosphorylation
Inflammation

Keywords

  • MAPK
  • NF-κB
  • Tobacco smoke
  • Transcription factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

@article{7b0ebe1c56694da48c9215122cfeb30c,
title = "Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells",
abstract = "Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.",
keywords = "MAPK, NF-κB, Tobacco smoke, Transcription factor",
author = "Jinming Zhao and Harper, {Richart W} and Aaron Barchowsky and Di, {Y. P Peter}",
year = "2007",
month = "8",
doi = "10.1152/ajplung.00345.2006",
language = "English (US)",
volume = "293",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Identification of multiple MAPK-mediated transcription factors regulated by tobacco smoke in airway epithelial cells

AU - Zhao, Jinming

AU - Harper, Richart W

AU - Barchowsky, Aaron

AU - Di, Y. P Peter

PY - 2007/8

Y1 - 2007/8

N2 - Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.

AB - Activation and regulation of transcription factors (TFs) are the major mechanisms regulating changes in gene expression upon environmental exposure. Tobacco smoke (TS) is a complex mixture of chemicals, each of which could act through different signal cascades, leading to the regulation of distinct TFs and alterations in subsequent gene expression. We proposed that TS exposure affects inflammatory gene expression at the transcriptional level by modulating the DNA binding activities of TFs. To investigate transcriptional regulation upon TS exposure, a protein/DNA array was applied to screen TFs that are affected by TS exposure. This array-based screening allowed us to simultaneously detect 244 different TFs. Our results indicated that multiple TFs were rapidly activated upon TS exposure. DNA-binding activity of differentially expressed TFs was confirmed by EMSA. Our results showed that at least 20 TFs displayed more than twofold expressional changes after smoke treatment. Ten smoke-induced TFs, including NF-κB, VDR, ISRE, and RSRFC4, were involved in MAPK signaling pathways. The NF-κB family, which is involved in inflammation-induced gene activation, was selected for further study to characterize TS exposure-induced transcriptional activation. Western blot analysis and immunofluorescence microscopy indicated that TS exposure induced phosphorylation of IκB and translocation of NF-κB p65/p50 heterodimers into the nucleus. This activity was abrogated by the MAPK inhibitors PD98059 and U0126. Our results confirmed that activation of MAPK signaling pathways by TS exposure increased transcriptional activity of NF-κB. These data provide a potential mechanism for TS-induced inflammatory gene expression.

KW - MAPK

KW - NF-κB

KW - Tobacco smoke

KW - Transcription factor

UR - http://www.scopus.com/inward/record.url?scp=34547616622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547616622&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00345.2006

DO - 10.1152/ajplung.00345.2006

M3 - Article

C2 - 17496060

AN - SCOPUS:34547616622

VL - 293

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 2

ER -