Related Experiment Video
Updated: Jul 5, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Alterations in the cardiac inflammatory response to burn trauma in mice lacking a functional Toll-like receptor 4
Brandon Bruns1, David Maass, Robert Barber
1Department of Surgery, UT Southwestern Medical Center at Dallas, Texas 75390-9063, USA.
Abstract:
Our group and others have previously shown that Toll-like receptor 4 (TLR-4) inactivation prevents burn-induced 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-kappaB was also characterized via electrophoretic mobility shift assay. Systemic and cardiac myocyte secretion of TNF-alpha, IL-1 beta, 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 burn-induced responses, including phosphorylation of p38 MAPK, nuclear translocation of nuclear factor-kappaB, 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.
Insights
Toll-like receptor 4 (TLR-4) inactivation protects the heart after burn injury by reducing inflammation. This study shows TLR-4 signaling is crucial for the cardiac inflammatory response to burns.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Toll-like receptor 4 (TLR-4) inactivation prevents burn-induced myocardial contractile dysfunction.
- The precise molecular mechanisms underlying this cardioprotection remain unclear.
Purpose of the Study:
- To investigate the role of TLR-4 in the cardiac inflammatory response following thermal injury.
- To elucidate the molecular pathways involved in burn-induced heart dysfunction.
Main Methods:
- Utilized C3H/HeJ (TLR-4 mutant) and C3H/HeN (wild-type) mice subjected to burn injury.
- Assessed myocardial inflammatory signaling via immunoblotting (p38 MAPK, NF-κB) and ELISA (cytokines).
- Evaluated nuclear factor-kappaB (NF-κB) activation using electrophoretic mobility shift assay.
Main Results:
- Burn injury in wild-type mice induced myocardial inflammation, increasing phosphorylated p38 MAPK and nuclear p50.
- Burn injury elevated systemic and cardiac myocyte secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).
- TLR-4 inactivation attenuated burn-induced p38 MAPK phosphorylation, NF-κB translocation, and cytokine secretion.
Conclusions:
- Burn injury triggers an inflammatory cascade in the heart mediated by TLR-4 and Toll/IL-1 signaling.
- This TLR-4-dependent cardiac inflammation contributes to myocardial injury and contractile dysfunction post-burn.
- Targeting TLR-4 may offer a therapeutic strategy for managing burn-related cardiac complications.
