Open AccessAlcohol alters IL-6 Signal Transduction in the CNS of Transgenic Mice with Increased Astrocyte Expression of IL-6
Author(s) -
Donna L. Gruol,
Claudia Melkonian,
Salvador HuitrónReséndiz,
Amanda J. Roberts
Publication year - 2020
Publication title -
cellular and molecular neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.255
H-Index - 90
eISSN - 1573-6830
pISSN - 0272-4340
DOI - 10.1007/s10571-020-00879-2
Subject(s) - signal transduction , stat protein , astrocyte , biology , stat3 , microbiology and biotechnology , activator (genetics) , mapk/erk pathway , central nervous system , transcription factor , endocrinology , receptor , biochemistry , gene
Neuroimmune factors, including the cytokine interleukin-6 (IL-6), are important chemical regulators of central nervous system (CNS) function under both physiological and pathological conditions. Elevated expression of IL-6 occurs in the CNS in a variety of disorders associated with altered CNS function, including excessive alcohol use. Alcohol-induced production of IL-6 has been reported for several CNS regions including the cerebellum. Cerebellar actions of alcohol occur through a variety of mechanisms, but alcohol-induced changes in signal transduction, transcription, and translation are known to play important roles. IL-6 is an activator of signal transduction that regulates gene expression. Thus, alcohol-induced IL-6 production could contribute to cerebellar effects of alcohol by altering gene expression, especially under conditions of chronic alcohol abuse, where IL-6 levels could be habitually elevated. To gain an understanding of the effects of alcohol on IL-6 signal transduction, we studied activation/expression of IL-6 signal transduction partners STAT3 (Signal Transducer and Activator of Transcription), CCAAT-enhancer binding protein (C/EBP) beta, and p42/p44 mitogen-activated protein kinase (MAPK) at the protein level. Cerebella of transgenic mice that express elevated levels of astrocyte produced IL-6 in the CNS were studied. Results show that the both IL-6 and chronic intermittent alcohol exposure/withdrawal affect IL-6 signal transduction partners and that the actions of IL-6 and alcohol interact to alter activation/expression of IL-6 signal transduction partners. The alcohol/IL-6 interactions may contribute to cerebellar actions of alcohol, whereas the effects of IL-6 alone may have relevance to cerebellar changes occurring in CNS disorders associated with elevated levels of IL-6.