help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 6, 2003, doi:10.1165/rcmb.2002-0126OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 1, July 2003, 124-132

A more recent version of this article appeared on July 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0126OCv1
29/1/124    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeshita, K.
Right arrow Articles by Yamaguchi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeshita, K.
Right arrow Articles by Yamaguchi, K.

Submitted on August 5, 2002
Revised on February 3, 2003

Hypercapnic Acidosis Attenuates Endotoxin-induced Nuclear Factor-{kappa}B Activation

Kei Takeshita1, Yukio Suzuki2, Kazumi Nishio3, Osamu Takeuchi4, Kyoko Toda4, Hiroyasu Kudo3, Naoki Miyao3, Makoto Ishii3, Nagato Sato3, Katsuhiko Naoki3, Takuya Aoki3, Koichi Suzuki3, Rika Hiraoka1, and Kazuhiro Yamaguchi3*

1 Department of Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan; Department of Medicine, Kitasato Institute Hospital, Minato, Tokyo, Japan, 2 Department of Medicine, Kitasato Institute Hospital, Minato, Tokyo, Japan, 3 Department of Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan, 4 Department of Biomedical Research, Kitasato Institute Hospital, Minato, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: yamaguc{at}cpnet.med.keio.ac.jp.

Although permissive hypercapnia improves the prognosis of patients with acute respiratory distress syndrome, it has not been conclusively determined whether hypercapnic acidosis (HA) is harmful or beneficial to sustained inflammation of the lung. The present study was designed to explore the molecular mechanism of HA in modifying lipopolysaccharide (LPS)-associated signals in pulmonary endothelial cells. LPS elicited degradation of inhibitory protein {kappa}B (I{kappa}B)-{alpha}, but not I{kappa}B-{beta}, resulting in activation of nuclear factor (NF)-{kappa}B in human pulmonary artery endothelial cells (HPAEC). Exposure to HA significantly attenuated LPS-induced NF-{kappa}B activation through suppressing I{kappa}B-{alpha} degradation. Isocapnic acidosis and buffered hypercapnia showed qualitatively similar but quantitatively smaller effects. HA did not lower the LPS-enhanced activation of activator protein (AP)-1. Following the reduced NF-{kappa}B activation, HA suppressed the mRNA and protein levels of intercellular adhesion molecule (ICAM)-1 and interleukin (IL)-8, resulting in a decrease in both LDH release into the medium and neutrophil adherence to LPS-activated HPAEC. In contrast, HA did not inhibit LPS-enhanced neutrophil expression of integrin, Mac-1. Based on these findings, we concluded that hypercapnic acidosis would have anti-inflammatory effects essentially through a mechanism inhibiting NF-{kappa}B activation, leading to downregulation of ICAM-1 and IL-8, which in turn inhibits neutrophil adherence to pulmonary endothelial cells.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
C.-S. Lin, J. G. Wann, C.-W. Hsiao, D. W. Tai, J.-S. Chen, Y.-H. Hsu, H.-C. Huang, and C.-F. Chao
Intracellular acidification enhances neutrophil phagocytosis in chronic haemodialysis patients: possible role of CD11b/CD18
Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1642 - 1649.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Z. Wang, F. Su, A. Bruhn, X. Yang, and J.-L. Vincent
Acute Hypercapnia Improves Indices of Tissue Oxygenation More than Dobutamine in Septic Shock
Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 178 - 183.
[Abstract] [Full Text] [PDF]

Home page
 NeoReviewsHome page
J. D. Miller and W. A. Carlo
Permissive Hypercapnia in Neonates
NeoReviews, August 1, 2007; 8(8): e345 - e353.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Kantores, P. J. McNamara, L. Teixeira, D. Engelberts, P. Murthy, B. P. Kavanagh, and R. P. Jankov
Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat
Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L912 - L922.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. Caironi, F. Ichinose, R. Liu, R. C. Jones, K. D. Bloch, and W. M. Zapol
5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury
Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 334 - 343.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. J. Lang, P. Dong, E. K. Hosszu, and I. R. Doyle
Effect of CO2 on LPS-induced cytokine responses in rat alveolar macrophages
Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L96 - L103.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. P. Kavanagh
Therapeutic Hypercapnia: Careful Science, Better Trials
Am. J. Respir. Crit. Care Med., January 15, 2005; 171(2): 96 - 97.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. D. Lang, M. Figueroa, K. D. Sanders, M. Aslan, Y. Liu, P. Chumley, and B. A. Freeman
Hypercapnia via Reduced Rate and Tidal Volume Contributes to Lipopolysaccharide-induced Lung Injury
Am. J. Respir. Crit. Care Med., January 15, 2005; 171(2): 147 - 157.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. G. Laffey, R. P. Jankov, D. Engelberts, A. K. Tanswell, M. Post, T. Lindsay, J. B. Mullen, A. Romaschin, D. Stephens, C. McKerlie, et al.
Effects of Therapeutic Hypercapnia on Mesenteric Ischemia-Reperfusion Injury
Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1383 - 1390.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society.