A systems biology approach reveals the dose- and time-dependent effect of primary human airway epithelium tissue culture after exposure to cigarette smoke in vitro

Bioinformatics and Biology Insights
Carole MathisJulia Hoeng

Abstract

To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using complementary computational approaches and an integrated mRNA-microRNA (miRNA) analysis. The main cellular pathways perturbed by CS exposure were related to stress responses (oxidative stress and xenobiotic metabolism), inflammation (inhibition of nuclear factor-κB and the interferon gamma-dependent pathway), and proliferation/differentiation. Within post-exposure periods up to 48 hours, a transient kinetic response was observed at lower CS doses, whereas higher doses resulted in more sustained responses. In conclusion, this systems toxicology approach has potential for product testing according to "21st Century Toxicology".

References

Jan 3, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·K TakeyamaJ A Nadel
Jan 3, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·S Gebel, T Müller
Apr 12, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Lorraine B Ware, Michael A Matthay
Apr 24, 2002·American Journal of Respiratory Cell and Molecular Biology·Yasushi SakamakiToshikazu Nakamura
May 29, 2003·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·H Fehrenbach
Aug 28, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Michaela AufderheideDetlef Ritter
Mar 19, 2004·The Journal of Biological Chemistry·Daniel W NebertFrank J Gonzalez
Jul 21, 2004·The Journal of Biological Chemistry·Erin GenschCarol Basbaum
Apr 29, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Wanda R FieldsDavid J Doolittle
Sep 27, 2005·Alternatives to Laboratory Animals : ATLA·Jeremy PhillipsEian Massey
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Mar 18, 2006·American Journal of Respiratory Cell and Molecular Biology·Tomasz K BaginskiDavid C Swinney
Oct 6, 2006·PLoS Medicine·Anju SinghShyam Biswal
Dec 27, 2006·Cancer Letters·Masanori Kitamura, Ayumi Kasai
Jan 16, 2007·Science·Brendan J Frey, Delbert Dueck
Jan 16, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Heather MaundersAudrey Richter
Aug 25, 2007·American Journal of Respiratory Cell and Molecular Biology·Sima AllahverdianDelbert R Dorscheid
Jan 23, 2008·Respiratory Research·Tomoko BetsuyakuMasaharu Nishimura
Aug 6, 2008·Expert Opinion on Drug Metabolism & Toxicology·Barbara Rothen-RutishauserPeter Gehr
Aug 12, 2008·Current Molecular Medicine·Sekhar P Reddy
Sep 17, 2008·Pharmacogenetics and Genomics·Keith SextonKelly A BéruBé
Jan 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Frank SchembriAvrum Spira
May 2, 2009·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Kwang-Hyuck LeeAnirban Maitra
Sep 30, 2009·Nucleic Acids Research·Juan WangQinghua Cui
Feb 6, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stephan GebelThomas Müller
Mar 20, 2010·The Journal of Biological Chemistry·Noureddine LoukiliLucas Liaudet
Jun 8, 2010·American Journal of Respiratory Cell and Molecular Biology·Anna DvorakRonald G Crystal
Oct 23, 2010·Molecular Cell·Anthony K L Leung, Phillip A Sharp
Oct 26, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alejandro A PezzuloJoseph Zabner
Nov 23, 2010·Nature Reviews. Immunology·Grace Y Chen, Gabriel Nuñez
Jan 13, 2011·The American Journal of Pathology·Ning ShenChao-Jun Li
Feb 19, 2011·Nature Reviews. Immunology·Luke A O'NeillClaire E McCoy
Mar 25, 2011·Respiration; International Review of Thoracic Diseases·Ian M AdcockPeter J Barnes
May 4, 2011·Environmental and Molecular Mutagenesis·Brinda MahadevanAnn M Richard
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov

❮ Previous
Next ❯

Citations

May 8, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Anne S KienhuisReinskje Talhout
Jul 30, 2016·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Xiang Li

❮ Previous
Next ❯

Datasets Mentioned

BETA
E-MTAB-874
E-MTAB-877

Methods Mentioned

BETA
protein array

Software Mentioned

limma
APcluster
GSEA
RCR
ArrayExpress
R

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.