TY - JOUR
T1 - Alterations in the cardiac inflammatory response to burn trauma in mice lacking a functional Toll-like receptor 4 gene
AU - Bruns, Brandon
AU - Maass, David
AU - Barber, Robert
AU - Horton, Jureta
AU - Carlson, Deborah
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2008/12
Y1 - 2008/12
N2 - Our group and others have previously shown that Toll-like receptor 4 (TLR-4) inactivation prevents buminduced myocardial contractile dysfunction; however, the molecular mechanisms that are involved in this cardioprotection are not well defined. This present study examines the involvement of TLR-4 in the cardiac inflammatory response to thermal insult. C3H/HeJ (TLR-4 mutant mice) and C3H/HeN wild-type (WT) mice were subjected to either a sham burn or 40% full-thickness burn injury and were fluid resuscitated with lactated Ringer using the Parkland formula. Mice (n = 7-9 per group) were killed at 2,4, or 24 h postsham or burn, and heart tissue was harvested. Immunoblotting was performed to evaluate phosphorylated p38 mitogen-activated protein kinase (MAPK), nuclear p50, and cytoplasmic p50. Nuclear factor-KB was also characterized via electrophoretic mobility shift assay. Systemic and cardiac myocyte secretion of TNF-α, IL-iβ, IL-6, and IL-10 were measured by enzyme-linked immunosorbent assay. Burn injury in WT mice promoted myocardial inflammatory signaling that included increased expression of phosphorylated p38 MAPK, nuclear p50, and increased cardiac myocyte secretion of cytokines. Systemic cytokines were also increased in WT animals, although not to the extent of the myocardial cytokine expression. Toll-like receptor 4 inactivation resulted in an attenuation of several buminduced responses, including phosphorylation of p38 MAPK, nuclear translocation of nuclear factor-κB, and cytokine secretion. These data suggest that burn injury initiates an inflammatory response via Toll/IL-1 signaling in the heart, which contributes to cardiac injury and contractile dysfunction.
AB - Our group and others have previously shown that Toll-like receptor 4 (TLR-4) inactivation prevents buminduced myocardial contractile dysfunction; however, the molecular mechanisms that are involved in this cardioprotection are not well defined. This present study examines the involvement of TLR-4 in the cardiac inflammatory response to thermal insult. C3H/HeJ (TLR-4 mutant mice) and C3H/HeN wild-type (WT) mice were subjected to either a sham burn or 40% full-thickness burn injury and were fluid resuscitated with lactated Ringer using the Parkland formula. Mice (n = 7-9 per group) were killed at 2,4, or 24 h postsham or burn, and heart tissue was harvested. Immunoblotting was performed to evaluate phosphorylated p38 mitogen-activated protein kinase (MAPK), nuclear p50, and cytoplasmic p50. Nuclear factor-KB was also characterized via electrophoretic mobility shift assay. Systemic and cardiac myocyte secretion of TNF-α, IL-iβ, IL-6, and IL-10 were measured by enzyme-linked immunosorbent assay. Burn injury in WT mice promoted myocardial inflammatory signaling that included increased expression of phosphorylated p38 MAPK, nuclear p50, and increased cardiac myocyte secretion of cytokines. Systemic cytokines were also increased in WT animals, although not to the extent of the myocardial cytokine expression. Toll-like receptor 4 inactivation resulted in an attenuation of several buminduced responses, including phosphorylation of p38 MAPK, nuclear translocation of nuclear factor-κB, and cytokine secretion. These data suggest that burn injury initiates an inflammatory response via Toll/IL-1 signaling in the heart, which contributes to cardiac injury and contractile dysfunction.
KW - Cardiac
KW - Cytokine
KW - Myocyte
KW - Nuclear factor-κB
KW - TNF-α
KW - p38 mitogen-activated protein kinase
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U2 - 10.1097/SHK.0b013e318173f329
DO - 10.1097/SHK.0b013e318173f329
M3 - Article
C2 - 18496236
AN - SCOPUS:58149251945
SN - 1073-2322
VL - 30
SP - 740
EP - 746
JO - Shock
JF - Shock
IS - 6
ER -