| First Author | Merrill JC | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 52 | Pages | 21247-52 |
| PubMed ID | 22160695 | Mgi Jnum | J:180147 |
| Mgi Id | MGI:5305524 | Doi | 10.1073/pnas.1111492108 |
| Citation | Merrill JC, et al. (2011) Whole-body deletion of LPS-induced TNF-alpha factor (LITAF) markedly improves experimental endotoxic shock and inflammatory arthritis. Proc Natl Acad Sci U S A 108(52):21247-52 |
| abstractText | LPS-induced TNF-alpha factor (LITAF) mediates cytokine expression in response to endotoxin challenge. Previously, we reported that macrophage-specific LITAF-deficient (macLITAF-/-) mice exposed to LPS have a delayed onset in the serum levels of proinflammatory cytokines and prolonged persistence of anti-inflammatory cytokines, but only partial protection from endotoxic shock. We postulated that greater protection might be achieved if LITAF were deleted from all LITAF-producing cells, including macrophages. Using a Cre-loxP system, we engineered a tamoxifen-induced recombination mouse [tamLITAF(i)-/-] that resulted in whole-body LITAF deficiency. Our findings demonstrate that (i) tamLITAF(i)-/- mice are more resistant to systemic Escherichia coli LPS-induced lethality than our previous macLITAF-/- mice, providing evidence that LITAF-producing cells other than LysMCre-positive cells play an important role in mediating endotoxic shock; (ii) tamLITAF(i)-/- mice show a similar pattern of cytokine expression with decreased proinflammatory and prolonged anti-inflammatory mediators compared with WT mice; and (iii) tamLITAF(i)-/- mice, compared with WT mice, display a significant reduction in bone resorption and inflammation associated with a local chronic inflammatory disease--namely, collagen antibody-induced arthritis. Our findings offer a unique model to study the role of LITAF in systemic and chronic local inflammatory processes, and pave the way for anti-LITAF therapeutic approaches for the treatment of TNF-mediated inflammatory diseases. |
