The systemic inflammatory response is involved in the regulation of K(+) channel expression in brain via TNF-alpha-dependent and -independent pathways

Vicente García, Rubén, 1978-; Coma Camprodón, Mireia; Busquets, Silvia; Moore Carrasco, Rodrigo; López Soriano, Francisco J.; Argilés, Josep M.; Felipe, Antonio

doi:http://dx.doi.org/10.1016/j.febslet.2004.07.030

The systemic inflammatory response is involved in the regulation of K(+) channel expression in brain via TNF-alpha-dependent and -independent pathways

Citation

Vicente R, Coma M, Busquets S, Moore-Carrasco R, López-Soriano FJ, Argilés JM et al. The systemic inflammatory response is involved in the regulation of K(+) channel expression in brain via TNF-alpha-dependent and -independent pathways. FEBS Letters. 2004;572(1-3):189-94. DOI: 10.1016/j.febslet.2004.07.030

Abstract

TNF-alpha, generated during the systemic inflammatory response, triggers a wide range of biological activities that mediate the neurologic manifestations associated with cancer and infection. Since this cytokine regulates ion channels in vitro (especially Kv1.3 and Kir2.1), we aimed to study Kv1.3 and Kir2.1 expression in brain in response to in vivo systemic inflammation. Cancer-induced cachexia and LPS administration increased plasma TNF-alpha. Kv1.3 and Kir2.1 expression was impaired in brain during cancer cachexia. However, LPS treatment induced Kv1.3 and downregulated Kir2.1 expression, and TNF-alpha administration mimicked these results. Experiments using TNF-alpha double receptor knockout mice demonstrated that the systemic inflammatory response mediates K(+) channel regulation in brain via TNF-alpha-dependent and -independent redundant pathways. In summary, distinct neurological alterations associated with systemic inflammation may result from the interaction of various cytokine pathways tuning ion channel expression in response to neurophysiological and neuroimmunological processes.