PMID- 10430608
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 3
DP  - 1999 Aug
TI  - Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium.
PG  - 271-80
AB  - Expression of innate immune response proteins, including IL-1beta, TNF, and the
      cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented 
      in the hearts of humans and experimental animals with heart failure regardless of
      etiology, although the proximal events leading to their expression are unknown.
      Noting that expression of a human homologue of Drosophila Toll, a proximal innate
      immunity transmembrane signaling protein in the fly, now termed human Toll-like
      receptor 4 (hTLR4), appeared to be relatively high in the heart, we examined TLR4
      mRNA and protein abundance in isolated cellular constituents of cardiac muscle
      and in normal and abnormal murine, rat, and human myocardium. TLR4 expression
      levels in cardiac myocytes and in coronary microvascular endothelial cells could 
      be enhanced by either LPS or IL-1beta, an effect inhibited by the oxygen radical 
      scavenger PDTC. Transfection of a constitutively active TLR4 construct,
      CD4/hTLR4, resulted in activation of a nuclear factor-kappaB reporter construct, 
      but not of an AP-1 or an iNOS reporter construct, in cardiac myocytes. In normal 
      murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably
      cytoplasmic, in cardiac myocytes. However, in remodeling murine myocardium remote
      from sites of ischemic injury and in heart tissue from patients with idiopathic
      dilated cardiomyopathy, focal areas of intense TLR4 staining were observed in
      juxtaposed regions of 2 or more adjacent myocytes; this staining was not observed
      in control myocardium. Increased expression and signaling by TLR4, and perhaps
      other Toll homologues, may contribute to the activation of innate immunity in
      injured myocardium.
FAU - Frantz, S
AU  - Frantz S
AD  - Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts
      02115, USA.
FAU - Kobzik, L
AU  - Kobzik L
FAU - Kim, Y D
AU  - Kim YD
FAU - Fukazawa, R
AU  - Fukazawa R
FAU - Medzhitov, R
AU  - Medzhitov R
FAU - Lee, R T
AU  - Lee RT
FAU - Kelly, R A
AU  - Kelly RA
LA  - eng
GR  - P50 HL052320/HL/NHLBI NIH HHS/United States
GR  - HL-36141/HL/NHLBI NIH HHS/United States
GR  - HL-52320/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CD4 Antigens)
RN  - 0 (DNA, Complementary)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Transcription Factor AP-1)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (NOS2 protein, human)
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)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
SB  - AIM
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CD4 Antigens/genetics
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - Coronary Vessels/cytology
MH  - DNA, Complementary/isolation & purification
MH  - *Drosophila Proteins
MH  - Gene Expression Regulation/immunology
MH  - Heart Failure/*metabolism/pathology
MH  - Heart Ventricles/cytology
MH  - Humans
MH  - Immunohistochemistry
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-1/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Membrane Glycoproteins/*biosynthesis/genetics/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Myocardial Infarction/metabolism/pathology
MH  - Myocardium/*metabolism/pathology
MH  - NF-kappa B/metabolism/physiology
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Organ Specificity/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cell Surface/*biosynthesis/genetics/physiology
MH  - Toll-Like Receptor 4
MH  - Toll-Like Receptors
MH  - Transcription Factor AP-1/metabolism
PMC - PMC408420
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - 10.1172/JCI6709 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Aug;104(3):271-80. doi: 10.1172/JCI6709.