Role of P38 Mitogen-Activated Protein Kinase in Lung Injury After Burn Trauma

Abstract

This study was undertaken to evaluate the effect of SB203580, a specific p38 mitogen-activated protein (MAP) kinase inhibitor, on burn-induced lung injury as well as the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in rats to characterize the role of p38 MAP kinase in lung injury after burn trauma. Sprague-Dawley rats were divided into three groups: 1) sham group, or rats who underwent sham burn; 2) control group, or rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; and 3) SB203580 group, or rats given burn injury and lactated Ringers solution with SB203580 inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis. TNF-alpha and IL-1beta protein in bronchoalveolar lavage fluid and serum were measured by enzyme-linked immunosorbent assay and p38 MAP kinase was activity determined in lung by Western blot analysis. These studies showed that significant activation of p38 MAP kinase at 24 h postburn compared with control. Burn trauma resulted in increased pulmonary capillary leakage permeability, elevated levels of TNF-alpha and IL-1beta in bronchoalveolar lavage fluid and serum, and worsened histologic condition. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-alpha and IL-1beta, and prevented burn-mediated lung injury. These data suggest that p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-alpha and IL-1beta and contributes to burn-induced lung injury.

Mammalian target of the rapamycin pathway is involved in non-alcoholic fatty liver disease

“…a balance between positive and negative regulation is important in modulating the function of irS-1. Previous studies have found that irS-1(Ser307) overphosphorylation may prevent the interconnection between irS-1 and insulin receptors and, therefore, may decrease irS-1 tyrosine phosphorylation (19,20). In line with previous findings, the results of this study showed significantly increased pIRS-1(Ser307) and considerably decreased pirS-1(Tyr102) levels in rat liver tissues when there was a pathomorphological progression from simple fatty liver (the HFd-8 group) to fatty hepatitis (the HFd-16 group).…”

Substance P Upregulates Cyclooxygenase-2 and Prostaglandin E Metabolite by Activating ERK1/2 and NF-κB in a Mouse Model of Burn-Induced Remote Acute Lung Injury

“…Studies have shown that p38 (67)(68)(69) and JNK (70,71) contribute to ALI after burn; furthermore, it has been reported that activation of p38 upregulates COX-2 levels in the gastrointestinal tract after burn (72), but not in the lungs. ERK1/2 has been implicated in many trauma or stress-related injury models, such as ischemic injury (73,74), hemorrhage (75), sepsis (34), and acute pancreatitis (76).…”

TLR4 Mediates Lung Injury and Inflammation in Intestinal Ischemia-Reperfusion

“…As we previously described [9], 10 mg/kg of fluorescein isothiocyanate (FITC)-labeled bovine albumin (Sigma-Aldrich, St. Louis, MO) was intravenously administrated to animals 2 h before the end of reperfusion. At the end of the experiments, mice were exsanguinated by cardiac puncture and serum was collected.…”