Expression of intestinal myeloid differentiation primary response protein 88 (Myd88) following experimental traumatic brain injury in a mouse model

Background: Traumatic brain injury (TBI) can cause gastrointestinal dysfunction and increase intestinal permeability. Nuclear factor kappa B (NF-kappa B) has been shown to be associated with these intestinal events, but it is not well known how NF-kappa B is activated in the intestine after TBI. Based on previous studies, we hypothesize that myeloid differentiation primary response protein 88 (Myd88) may have an important role in NF-kappa B activation in the intestine, which mediates the inflammation and ultimately results in acute intestinal mucosal injury. Methods: We randomly divided adult male C57BL/6 mice into control groups and TBI groups at different time points. We induced a closed head injury model by weight drop (a 333-g metal rod dropping from a 2.5-cm height). We detected Myd88 protein level and NF-kappa B binding activity in ileum tissue by Western blot and electrophoretic mobility shift assay, respectively. Meanwhile, we detected the mRNA levels of Myd88, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and intercellular adhesion molecule-1 by real-time polymerase chain reaction. Results: The Myd88 protein and mRNA levels, as well as NF-kappa B binding activity in the ileum tissue, significantly increased at 6 h after TBI, peaked at 3 d, and remained elevated by 5 d post-injury. The levels of TNF-alpha, IL-1 beta, and intercellular adhesion molecule-1 also remarkably increased after TBI. There was a positive relationship between the expression of Myd88 and that of NF-kappa B, TNF-alpha, and IL-1 beta. Conclusions: Traumatic brain injury induced a rapid and persistent up-regulation of Myd88, NF-kappa B, and proinflammatory cytokines in the intestine. This up-regulation which might have an important role in the pathogenesis of acute intestinal mucosal injury. (C) 2013 Elsevier Inc. All rights reserved.