| First Author | Pryhuber GS | Year | 2005 |
| Journal | Am J Pathol | Volume | 166 |
| Issue | 6 | Pages | 1637-45 |
| PubMed ID | 15920149 | Mgi Jnum | J:98818 |
| Mgi Id | MGI:3579972 | Doi | 10.1016/s0002-9440(10)62474-1 |
| Citation | Pryhuber GS, et al. (2005) Acute Tumor Necrosis Factor-{alpha}-Induced Liver Injury in the Absence of Tumor Necrosis Factor Receptor-Associated Factor 1 Gene Expression. Am J Pathol 166(6):1637-45 |
| abstractText | Pulmonary and serum levels of tumor necrosis factor-alpha (TNF-alpha), are elevated in many lung diseases, causing local inflammation, fever, and multiorgan, including hepatic, dysfunction. Cellular responses to TNF-alpha are determined by recruitment of specific proteins to intracellular receptor signaling complexes. One of these proteins, TNF receptor-associated factor 1 (TRAF1), is highly regulated in pulmonary cells. To determine the effect of reduced pulmonary TRAF1 expression, TRAF1-null (-/-) and control, BALB/c (wild-type), mice were treated intratracheally, intraperitoneally, or intravenously, with TNF-alpha. Despite relatively mild lung injury, intratracheal TNF-alpha-treated TRAF1-/- mice exhibited marked liver injury with an approximate fivefold increase in serum liver enzyme levels as compared to wild-type mice. In addition, serum TNF-alpha levels were strikingly elevated in TRAF1-/- mice. Pretreatment with neutralizing anti-TNFRI antibody significantly reduced liver injury and serum TNF-alpha. Cells isolated by bronchoalveolar lavage from intratracheally treated TRAF1-/- mice produced more TNF-alpha than cells from treated wild-type mice, suggesting that lung cells contributed to elevated serum TNF-alpha. These studies suggest that TRAF1 provides negative feedback for TNF-alpha synthesis and limits TNFRI-mediated systemic effects of TNF-alpha originating in the lung. |
