NYMC Faculty Publications
Whole-Body Deletion of LPS-Induced TNF-α Factor (LITAF) Markedly Improves Experimental Endotoxic Shock and Inflammatory Arthritis
Author Type(s)
Faculty
Additional Author Affiliation
Touro College of Dental Medicine at NYMC
DOI
10.1073/pnas.1111492108
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
First Page
21247
Last Page
21252
Document Type
Article
Publication Date
12-27-2011
Department
Pharmacology
Abstract
LPS-induced TNF-α 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.
Recommended Citation
Merrill, J., You, J., Constable, C., Leeman, S., & Amar, S. (2011). Whole-Body Deletion of LPS-Induced TNF-α Factor (LITAF) Markedly Improves Experimental Endotoxic Shock and Inflammatory Arthritis. Proceedings of the National Academy of Sciences of the United States of America, 108 (52), 21247-21252. https://doi.org/10.1073/pnas.1111492108
