We have characterized mice with TNF ablation in macrophages/neutrophils, T cells or B cells in several pathophysiological models. We are in the process of generating a similar panel for LTa cytokine. TNF produced by T cells plays an important and non-redundant role in both host defense (Listeria, TB) and in autoimmune liver injury induced by ConA. Ablation of either TNF, or LTa fails to modulate the frequency of spontaneous tumors in mice with p53 null background, suggesting that increased frequency of lymphoma in patients on continuous TNF blockers may not be directly related to TNF.
| Komarova, Elena A; Krivokrysenko, Vadim; Wang, Kaihua et al. (2005) p53 is a suppressor of inflammatory response in mice. FASEB J 19:1030-2 |
| Cataisson, Christophe; Pearson, Andrea J; Torgerson, Sara et al. (2005) Protein kinase C alpha-mediated chemotaxis of neutrophils requires NF-kappa B activity but is independent of TNF alpha signaling in mouse skin in vivo. J Immunol 174:1686-92 |
| Grivennikov, Sergei I; Tumanov, Alexei V; Liepinsh, Dmitry J et al. (2005) Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects. Immunity 22:93-104 |
| Lin, Yong; Choksi, Swati; Shen, Han-Ming et al. (2004) Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem 279:10822-8 |
