Medicine and Health Sciences Commons^™

Inflammation, Organomegaly, And Muscle Wasting Despite Hyperphagia In A Mouse Model Of Burn Cachexia., Felipe E Pedroso, Paul B Spalding, Michael C Cheung, Relin Yang, Juan C Gutierrez, Andrea Bonetto, Rui Zhan, Ho Lam Chan, Nicholas Namias, Leonidas G Koniaris, Teresa A Zimmers

Department of Cancer Biology Faculty Papers

BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking.

METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and …

Inflammatory Signaling Compromises Cell Responses To Interferon Alpha., W-C Huangfu, J Qian, C Liu, J Liu, A E Lokshin, D P Baker, H Rui, S Y Fuchs

Department of Cancer Biology Faculty Papers

Interferon alpha (IFNα) is widely used for treatment of melanoma and certain other malignancies. This cytokine as well as the related IFNβ exerts potent anti-tumorigenic effects; however, their efficacy in patients is often suboptimal. Here, we report that inflammatory signaling impedes the effects of IFNα/β. Melanoma cells can secrete pro-inflammatory cytokines that inhibit cellular responses to IFNα/β via activating the ligand-independent pathway for the phosphorylation and subsequent ubiquitination and accelerated degradation of the IFNAR1 chain of type I IFN receptor. Catalytic activity of the p38 protein kinase was required for IFNAR1 downregulation and inhibition of IFNα/β signaling induced by proinflammatory …

Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman

Center for Translational Medicine Faculty Papers

Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A(1)-R, A(2A)-R and A(3)-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A(2A)-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A(2A)-R in FVB …