The Journal of Immunology, 2008,
180,
5761
Copyright © 2008 by The American Association of Immunologists, Inc.
Response to Comment on "Cigarette Smoke-Induced Pulmonary Inflammation Is TLR4/MyD88 and IL-1R1/MyD88 Signaling Dependent"
Emilie Doz,
Bernhard Ryffel,
Valérie F. J. Quesniaux and
Isabelle Couillin
Molecular Immunology and Embryology, Unité Mixe de Recherche 6218, University of Orleans and Centre National de la Recherche Scientifique, Orleans, France
We investigated the role of TLR4 and MyD88 signaling in an acute cigarette smoke-induced lung inflammation and found that the heat shock protein 70 is up-regulated and is a likely candidate activating TLR4 leading to lung inflammation (1). These findings agree with those of Maes et al. (2), showing that subacute cigarette smoke exposure in TLR4-defective mice results in a reduced pulmonary inflammation. We extended the study to demonstrate that IL-1 is induced in vitro and in vivo after cigarette smoke exposure and that IL-1R1/MyD88 signaling is critical for the acute inflammatory response (1). Furthermore, the findings by Maes et al. (2) indicate that during chronic cigarette exposure TLR4 signaling is less important and point to other as yet unidentified pathways leading to chronic inflammation and emphysema, which were not investigated. IL-1 induced in vivo after cigarette smoke exposure may contribute to this chronic inflammation and emphysema through IL-1R1/MyD88 signaling. Thus, the demonstration of Maes et al. (2) that beyond TLR4-dependent subacute smoke lung inflammation the development of chronic obstructive pulmonary disease is TLR4 independent raises the important point that the signaling pathways leading to acute or chronic disease may differ.
References
- Doz, E., N. Noulin, E. Boichot, I. Guénon, L. Fick, M. Le Bert, V. Lagente, B. Ryffel, B. Schnyder, V. F. J. Quesniaux, I. Couillin. 2008. Cigarette smoke-induced pulmonary inflammation is TLR4/MyD88 and IL-1R1/MyD88 signaling dependent. J. Immunol. 180: 1169-1178. [Abstract/Free Full Text]
- Maes, T., K. R. Bracke, K. Y. Vermaelen, I. K. Demedts, G. F. Joos, R. A. Pauwels, G. G. Brusselle. 2006. Murine TLR4 is implicated in cigarette smoke-induced pulmonary inflammation. Int. Arch. Allergy Immunol. 141: 354-368. [Medline]
