Lipopolysaccharide-induced Immune Responses in Relation to the TLR4(Asp299Gly) Gene Polymorphism

Overview

Journal Clin Vaccine Immunol

Publisher American Society for Microbiology

Specialties Allergy & Immunology
Pathology

Date 2008 Oct 18

PMID 18927069

Citations 6

Authors

Anna Lundberg

Lars Andersson Wikberg

Jorma Ilonen

Outi Vaarala

Malin Fageras Bottcher

Affiliations

Soon will be listed here.

Abstract

Altered microbial exposure is a possible explanation for the increase of allergies in the Western world. However, genetic factors influence microbially induced immune responses. We have investigated the TLR4(Asp299Gly) gene polymorphism and its possible association with receptor expression of circulating peripheral blood monocytes and the in vitro cytokine responses and phosphorylation of intracellular signaling proteins in peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) from Escherichia coli and Salmonella enterica serotype Typhimurium. We studied 34 of the predominant haplotype TLR4 Asp299 (AA) and 8 heterozygote Asp299Gly (AG) individuals. TLR4 expression levels were similar in the two genotype groups. Serovar Typhimurium LPS induced interleukin-12p70 from PBMC, and the degree of phosphorylation of the intracellular signaling protein IkappaBalpha in PBMC was lower in the AG than the AA group (P=0.03 and P=0.04, respectively). These results were not seen, however, when PMBC were stimulated with E. coli-derived LPS. Based on these results, we propose that TLR4(Asp299Gly) gene polymorphism and the bacterial origin of LPS should be considered when environmental LPS exposure is evaluated in disease risk or protection.

Citing Articles

Comparative Analysis of Intestinal TLR4 Gene Expression and Functional Verification in Lepus yarkandensis and Oryctolagus cuniculus.

Zhang L, Shao D, You J, Liu P, Deng F, Zhang J Biochem Genet. 2024; .

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The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer.

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Toll-like receptor polymorphisms compromise the inflammatory response against bacterial antigen translocation in cirrhosis.

Pinero P, Juanola O, Caparros E, Zapater P, Gimenez P, Gonzalez-Navajas J Sci Rep. 2017; 7:46425.

PMID: 28418003 PMC: 5394473. DOI: 10.1038/srep46425.

The Toll-like receptor 4 polymorphism Asp299Gly but not Thr399Ile influences TLR4 signaling and function.

Long H, OConnor B, Zemans R, Zhou X, Yang I, Schwartz D PLoS One. 2014; 9(4):e93550.

PMID: 24695807 PMC: 3973565. DOI: 10.1371/journal.pone.0093550.

Toll-like receptor polymorphisms, inflammatory and infectious diseases, allergies, and cancer.

Medvedev A J Interferon Cytokine Res. 2013; 33(9):467-84.

PMID: 23675778 PMC: 3760066. DOI: 10.1089/jir.2012.0140.

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