In vivo expression of proinflammatory mediators in the adult heart after endotoxin administration: the role of toll-like receptor-4

G Baumgarten; P Knuefermann; N Nozaki; N Sivasubramanian; D L Mann; J G Vallejo

doi:10.1086/320712

In vivo expression of proinflammatory mediators in the adult heart after endotoxin administration: the role of toll-like receptor-4

J Infect Dis. 2001 Jun 1;183(11):1617-24. doi: 10.1086/320712. Epub 2001 Apr 23.

Authors

G Baumgarten¹, P Knuefermann, N Nozaki, N Sivasubramanian, D L Mann, J G Vallejo

Affiliation

¹ Department of Medicine, Cardiology Section, Winters Center for Heart Failure Research, and Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA.

PMID: 11343210
DOI: 10.1086/320712

Abstract

Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO) may play a role in lipopolysaccharide (LPS)-induced cardiac depression. Toll-like receptor-4 (TLR-4) mediates the cytokine response to LPS in immune cells. TLR-4 also is expressed in human and murine myocardial tissue. Therefore, the hypothesis that LPS induces proinflammatory cytokines in the heart via TLR-4 was tested. C3H/HeJ (TLR-4 deficient) and C3HeB/FeJ mice were studied. LPS induced a robust increase in myocardial TNF-alpha and IL-1beta mRNA in C3HeB/FeJ mice. The response in C3H/HeJ mice was blunted and delayed. Myocardial TNF-alpha and IL-1beta protein levels were higher in C3HeB/FeJ mice, as were inducible NO synthase protein and NO production. Activation of myocardial NF-kappaB was observed within 30 min in C3HeB/FeJ mice but not in C3H/HeJ mice. These findings suggest that myocardial TLR-4 is involved in signaling cytokine production within the heart during endotoxic shock.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Drosophila Proteins*
Endotoxins / pharmacology*
Heart / drug effects*
Interleukin-1 / metabolism
Lipopolysaccharides
Membrane Glycoproteins / deficiency
Membrane Glycoproteins / genetics
Membrane Glycoproteins / physiology*
Mice
Mice, Inbred C3H
Mice, Knockout
Myocardium / metabolism*
NF-kappa B / metabolism
Nitric Oxide / metabolism
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type II
Receptors, Cell Surface / deficiency
Receptors, Cell Surface / genetics
Receptors, Cell Surface / physiology*
Signal Transduction
Time Factors
Toll-Like Receptor 4
Toll-Like Receptors
Tumor Necrosis Factor-alpha / metabolism

Substances

Drosophila Proteins
Endotoxins
Interleukin-1
Lipopolysaccharides
Membrane Glycoproteins
NF-kappa B
Receptors, Cell Surface
Toll-Like Receptor 4
Toll-Like Receptors
Tumor Necrosis Factor-alpha
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse