Logo image
Back
Genes other than TLR4 are involved in the response to inhaled LPS
Journal article   Open access   Peer reviewed

Genes other than TLR4 are involved in the response to inhaled LPS

Eva Lorenz, Michael Jones, Christine Wohlford-Lenane, Nicole Meyer, Kathy L Frees, Nancy C Arbour and David A Schwartz
American journal of physiology. Lung cellular and molecular physiology, Vol.281(5), pp.L1106-L1114
11/2001
DOI: 10.1152/ajplung.2001.281.5.L1106
PMID: 11597901
url
https://doi.org/10.1152/ajplung.2001.281.5.L1106View
Published (Version of record) Open Access

Abstract

For several decades, the mouse strains C3H/HeJ and C57BL/10ScNCr have been known to be hyporesponsive to endotoxin or lipopolysaccharide (LPS). Recently, mutations in Toll-like receptor (TLR) 4 have been shown to underlie this aberrant response to LPS. To further determine the relationship between TLR4 and responsiveness to LPS, we genotyped 18 strains of mice for TLR4 and evaluated the physiological and biological responses of these strains to inhaled LPS. Of the 18 strains tested, 6 were wild type for TLR4 and 12 had mutations in TLR4. Of those strains with TLR4 mutations, nine had mutations in highly conserved residues. Among the strains wild type for TLR4, the inflammatory response in the airway induced by inhalation of LPS showed a phenotype ranging from very sensitive (DBA/2) to hyporesponsive (C57BL/6). A broad spectrum of airway hyperreactivity after inhalation of LPS was also observed among strains wild type for TLR4. Although the TLR4 mutant strains C3H/HeJ and C57BL/10ScNCr were phenotypically distinct from the other strains with mutations in the TLR4 gene, the other strains with mutations for TLR4 demonstrated a broad distribution in their physiological and biological responses to inhaled LPS. The results of our study indicate that although certain TLR4 mutations can be linked to a change in the LPS response phenotype, additional genes are clearly involved in determining the physiological and biological responses to inhaled LPS in mammals.
 Tumor Necrosis Factor-alpha - metabolism Toll-Like Receptor 4 Membrane Glycoproteins - metabolism Humans Bronchial Provocation Tests Bronchi - drug effects Toll-Like Receptors Inhalation Exposure Methacholine Chloride - pharmacology Bronchi - metabolism Bronchoalveolar Lavage Fluid - cytology Drosophila Proteins Plethysmography, Whole Body Receptors, Cell Surface - metabolism Genotype Mice, Inbred Strains Membrane Glycoproteins - genetics Intercellular Adhesion Molecule-1 - metabolism Animals Lipopolysaccharides - pharmacology Chemokine CXCL2 Bronchoconstrictor Agents - pharmacology Chemokines - metabolism Mice Bronchoalveolar Lavage Fluid - chemistry Receptors, Cell Surface - genetics

Details

Metrics

24 Record Views
70 Times Cited - Web of Science
Logo image