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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/L657    most recent 90460.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Abolhassani, M. Articles by Schwartz, L. Search for Related Content PubMed PubMed Citation Articles by Abolhassani, M. Articles by Schwartz, L.

Carbon dioxide inhalation causes pulmonary inflammation

¹BCG Department, Pasteur Institute of Iran, Tehran, Iran; and ²Biorébus, Paris; ³Université Paris-Sud, EA4046, UFR de Bicêtre, Le Kremlin-Bicêtre; ⁴AP-HP, CHU de Bicêtre, Service de Biophysique et de Médecine Nucléaire, France; ⁵Epidemiology for Cancer Prevention, INSERM U897, ISPED, Victor Segalen Bordeaux 2 University, Bordeaux, France; and ⁶Service de Radiothérapie, Hôpital Pitié-Salpétrière, Paris, France

Submitted 27 August 2008 ; accepted in final form 8 January 2009

The aim of this study was to assess whether one of the most common poisons of cellular respiration, i.e., carbon dioxide, is proinflammatory. CO₂ is naturally present in the atmosphere at the level of 0.038% and involved in numerous cellular biochemical reactions. We analyzed in vitro the inflammation response induced by exposure to CO₂ for 48 h (0–20% with a constant O₂ concentration of 21%). In vivo mice were submitted to increasing concentrations of CO₂ (0, 5, 10, and 15% with a constant O₂ concentration of 21%) for 1 h. The exposure to concentrations above 5% of CO₂ resulted in the increased transcription (RNase protection assay) and secretion (ELISA) of proinflammatory cytokines [macrophage inflammatory protein-1 (MIP-1), MIP-1β, MIP-2, IL-8, IL-6, monocyte chemoattractant protein-1, and regulated upon activation, normal T cell expressed, and, presumably, secreted (RANTES)] by epithelial cell lines HT-29 or A549 and primary pulmonary cells retrieved from the exposed mice. Lung inflammation was also demonstrated in vivo by mucin 5AC-enhanced production and airway hyperreactivity induction. This response was mostly mediated by the nuclear translocation of p65 NF-B, itself a consequence of protein phosphatase 2A (PP2A) activation. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reversed the effect of carbon dioxide, i.e., disrupted the NF-B activation and the proinflammatory cytokine secretion. In conclusion, this study strongly suggests that exposure to carbon dioxide may be more toxic than previously thought. This may be relevant for carcinogenic effects of combustion products.

tobacco smoke; protein phosphatase 2A; nuclear factor-B