Premium
Tonicity‐responsive enhancer binding protein (TonEBP) regulates TNF‐α‐induced hypothalamic inflammation
Author(s) -
Kim Han Rae,
Kim Dong Hee,
Kim Kwang Kon,
Jeong Bora,
Kang Dasol,
Lee Tae Hwan,
Park Jeong Woo,
Kwon Hyug Moo,
Lee Byung Ju
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13533
Subject(s) - enhancer , inflammation , chemistry , microbiology and biotechnology , tonicity , tumor necrosis factor alpha , endocrinology , biology , biochemistry , immunology , transcription factor , gene
Tonicity‐responsive enhancer binding protein (TonEBP) is a widely expressed transcription factor and is important in the regulation of inflammatory cytokines. Here, we have identified TonEBP expression in the hypothalamus, which is particularly high in proopiomelanocortin (POMC) neurons. TonEBP overexpression stimulates POMC transcription, and TonEBP haploinsufficiency in TonEBP (+/−) mice results in a decrease in hypothalamic POMC expression. TonEBP (+/−) mice show reduced sickness responses, which include anorexia and hyperthermia, that are initially induced by tumor necrosis factor (TNF)‐α. TonEBP (+/−) mice also show lower levels of TNF‐α‐induced hypothalamic expression of POMC and pro‐inflammatory cytokines. These results suggest that TonEBP is an important molecular regulator in the development of inflammatory sickness responses through the control of POMC and pro‐inflammatory cytokine expression in the hypothalamus.