PMID- 11343210 OWN - NLM STAT- MEDLINE DCOM- 20010621 LR - 20131121 IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 183 IP - 11 DP - 2001 Jun 1 TI - In vivo expression of proinflammatory mediators in the adult heart after endotoxin administration: the role of toll-like receptor-4. PG - 1617-24 AB - 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. FAU - Baumgarten, G AU - Baumgarten G AD - Department of Medicine, Cardiology Section, Winters Center for Heart Failure Research, and Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas, USA. FAU - Knuefermann, P AU - Knuefermann P FAU - Nozaki, N AU - Nozaki N FAU - Sivasubramanian, N AU - Sivasubramanian N FAU - Mann, D L AU - Mann DL FAU - Vallejo, J G AU - Vallejo JG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20010423 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Drosophila Proteins) RN - 0 (Endotoxins) RN - 0 (Interleukin-1) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (Receptors, Cell Surface) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) SB - IM MH - Animals MH - *Drosophila Proteins MH - Endotoxins/*pharmacology MH - Heart/*drug effects MH - Interleukin-1/metabolism MH - Lipopolysaccharides MH - Membrane Glycoproteins/deficiency/genetics/*physiology MH - Mice MH - Mice, Inbred C3H MH - Mice, Knockout MH - Myocardium/*metabolism MH - NF-kappa B/metabolism MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase/metabolism MH - Nitric Oxide Synthase Type II MH - Receptors, Cell Surface/deficiency/genetics/*physiology MH - Signal Transduction MH - Time Factors MH - Toll-Like Receptor 4 MH - Toll-Like Receptors MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2001/05/09 10:00 MHDA- 2001/06/22 10:01 CRDT- 2001/05/09 10:00 PHST- 2000/12/11 00:00 [received] PHST- 2001/02/26 00:00 [revised] PHST- 2001/05/09 10:00 [pubmed] PHST- 2001/06/22 10:01 [medline] PHST- 2001/05/09 10:00 [entrez] AID - JID001477 [pii] AID - 10.1086/320712 [doi] PST - ppublish SO - J Infect Dis. 2001 Jun 1;183(11):1617-24. doi: 10.1086/320712. Epub 2001 Apr 23.