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Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-[kappa]B activation
Kei Takeshita1, Yukio Suzuki, Kazumi Nishio
1Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
American Journal of Respiratory Cell and Molecular Biology
|February 26, 2003
Summary
Hypercapnic acidosis (HA) reduces lung inflammation by inhibiting nuclear factor-kappaB (NF-kappaB) activation. This mechanism downregulates key inflammatory molecules, decreasing neutrophil adherence to pulmonary endothelial cells.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Inflammation Research
Background:
- Permissive hypercapnia aids acute respiratory distress syndrome prognosis.
- The role of hypercapnic acidosis (HA) in lung inflammation remains unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of HA in modulating lipopolysaccharide (LPS)-induced inflammatory signals in pulmonary endothelial cells.
Main Methods:
- Human pulmonary artery endothelial cells were exposed to LPS and HA.
- Analyzed nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) activation.
- Quantified mRNA and protein levels of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8).
- Assessed lactate dehydrogenase release and neutrophil adherence.
Main Results:
- HA attenuated LPS-induced NF-kappaB activation by inhibiting IkappaB-alpha degradation.
- HA suppressed mRNA and protein expression of ICAM-1 and IL-8.
- Reduced neutrophil adherence to LPS-activated endothelial cells was observed.
- HA did not affect LPS-enhanced AP-1 activation or neutrophil Mac-1 expression.
Conclusions:
- Hypercapnic acidosis exhibits anti-inflammatory effects in the lungs.
- The primary mechanism involves the inhibition of NF-kappaB activation.
- This leads to reduced expression of ICAM-1 and IL-8, consequently decreasing neutrophil adherence.