TY - JOUR
T1 - In vivo expression of proinflammatory mediators in the adult heart after endotoxin administration
T2 - The role of toll-like receptor-4
AU - Baumgarten, Georg
AU - Knuefermann, Pascal
AU - Nozaki, Naoki
AU - Sivasubramanian, Natarajan
AU - Mann, Douglas L.
AU - Vallejo, Jesus G.
N1 - Funding Information:
Financial support: Minority Medical Faculty Development Program of the Robert Wood Johnson Foundation (029212 to J.G.V.); Deutsche Herz-stiftung (to G.B.); Deutsche Forschungsgemeinschaft (KN521/1-1 to P.K.).
PY - 2001/6/1
Y1 - 2001/6/1
N2 - Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, 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-α and IL-β mRNA in C3HeB/FeJ mice. The response in C3H/HeJ mice was blunted and delayed. Myocardial TNF- and IL-β protein levels were higher in C3HeB/FeJ mice, as were inducible NO synthase protein and NO production. Activation of myocardial NF-κB 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.
AB - Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, 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-α and IL-β mRNA in C3HeB/FeJ mice. The response in C3H/HeJ mice was blunted and delayed. Myocardial TNF- and IL-β protein levels were higher in C3HeB/FeJ mice, as were inducible NO synthase protein and NO production. Activation of myocardial NF-κB 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.
UR - http://www.scopus.com/inward/record.url?scp=0035371187&partnerID=8YFLogxK
U2 - 10.1086/320712
DO - 10.1086/320712
M3 - Article
C2 - 11343210
AN - SCOPUS:0035371187
SN - 0022-1899
VL - 183
SP - 1617
EP - 1624
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -