Tonicity-responsive enhancer binding protein (TonEBP) regulates TNF-α-induced hypothalamic inflammation.
hypothalamus
inflammation
proopiomelanocortin
sickness responses
tonicity-responsive enhancer binding protein
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
18
04
2019
revised:
19
06
2019
accepted:
30
06
2019
pubmed:
10
7
2019
medline:
19
6
2020
entrez:
9
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31281956
doi: 10.1002/1873-3468.13533
doi:
Substances chimiques
Nfat5 protein, mouse
0
Transcription Factors
0
Tumor Necrosis Factor-alpha
0
Pro-Opiomelanocortin
66796-54-1
Banques de données
GENBANK
['X03171.1']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2762-2770Subventions
Organisme : National Research Foundation of Korea
ID : 2014R1A6A1030318
Pays : International
Organisme : National Research Foundation of Korea
ID : NRF-2018R1D1A1B07046848
Pays : International
Organisme : National Research Foundation of Korea
ID : NRF-2013R1A1A2062093
Pays : International
Informations de copyright
© 2019 Federation of European Biochemical Societies.
Références
Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE and Schwartz MW (2013) Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes 62, 2629-2634.
Burfeind KG, Michaelis KA and Marks DL (2016) The central role of hypothalamic inflammation in the acute illness response and cachexia. Semin Cell Dev Biol 54, 42-52.
Jeong JK, Kim JG and Lee BJ (2014) Participation of the central melanocortin system in metabolic regulation and energy homeostasis. Cell Mol Life Sci 71, 3799-3809.
Valdearcos M, Xu AW and Koliwad SK (2015) Hypothalamic inflammation in the control of metabolic function. Annu Rev Physiol 77, 131-160.
Olmos G and Lladó J (2014) Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm 2014, e861231.
Purkayastha S, Zhang G and Cai D (2011) Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-beta and NF-kappaB. Nat Med 17, 883-887.
Bradley JR (2008) TNF-mediated inflammatory diseases. J Pathol 214, 149-160.
Hayden MS and Ghosh S (2004) Signaling to NF-kappaB. Genes Dev 18, 2195-2224.
Lawrence T (2009) The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 1, a001651.
Miyakawa H, Woo SK, Dahl SC, Handler JS and Kwon HM (1999) Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity. Proc Natl Acad Sci USA 96, 2538-2542.
Roth I, Leroy V, Kwon HM, Martin PY, Féraille E and Hasler U (2010) Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-kappaB activity. Mol Biol Cell 21, 3459-3474.
Stroud JC, Lopez-Rodriguez C, Rao A and Chen L (2002) Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor. Nat Struct Biol 9, 90-94.
Masuda K, Masuda R, Neidhart M, Simmen BR, Michel BA, Müller-Ladner U, Gay RE and Gay S (2002) Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the stage of proliferation. Arthritis Res 4, R8.
Halterman JA, Kwon HM, Leitinger N and Wamhoff BR (2012) NFAT5 expression in bone marrow-derived cells enhances atherosclerosis and drives macrophage migration. Front Physiol 3, 313.
Shin HJ, Kim H, Heo RW, Kim HJ, Choi WS, Kwon HM and Roh GS (2014) Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-kappaB-mediated neuroinflammation in kainic acid-induced seizures. Cell Death Differ 21, 1095-1106.
Paxinos G and Franklin KBJ (2001). The Mouse Brain in Stereotaxic Coordinates. (2 eds). Academic Press, San Diego.
Bluthé RM, Kelley KW and Dantzer R (2006) Effects of insulin-like growth factor-I on cytokine-induced sickness behavior in mice. Brain Behav Immun 20, 57-63.
Palina K, Bluthé RM, McCusker RH, Moos F, Dantzer R and Kelley KW (2007) TNFα-induced sickness behavior in mice with functional 55 kD TNF receptors is blocked by central IGF-I. J Neuroimmunol 187, 55-60.
Park BS, Jin SH, Park JJ, Park JW, Namgoong IS, Kim YI, Lee BJ and Kim JG (2011) Visfatin induces sickness responses in the brain. PLoS ONE 20, e15981.
Sanz E, Yang L, Su T, Morris DR, McKnight GS and Amieux PS (2009) Cell-type-specific isolation of ribosome-associated mRNA from complex tissues. Proc Natl Acad Sci USA 106, 13939-13944.
Heiman M, Schaefer A, Gong S, Peterson JD, Day M, Ramsey KE, Suárez-Fariñas M, Schwarz C, Stephan DA, Surmeier DJ, et al. (2008) Translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738-748.
Doyle JP, Dougherty JD, Heiman M, Schmidt EF, Stevens TR, Ma G, Bupp S, Shrestha P, Shah RD, Doughty ML, et al. (2008) Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell 135, 749-762.
Belsham DD, Fick LJ, Dalvi PS, Centeno ML, Chalmers JA, Lee PK, Wang Y, Drucker DJ and Koletar MM (2009) Ciliary neurotrophic factor recruitment of glucagon-like peptide-1 mediates neurogenesis, allowing immortalization of adult murine hypothalamic neurons. FASEB J 23, 4256-4265.
Kim JG, Park BS, Yun CH, Kim HJ, Kang SS, D'Elia AV, Damante G, Lee KU, Park JW, Kim ES, et al. (2011) Thyroid transcription factor-1 regulates feeding behavior via melanocortin pathway in the hypothalamus. Diabetes 60, 710-719.
Lee HH, Sanada S, An SM, Ye BJ, Lee JH, Seo YK, Lee C, Lee-Kwon W, Küper C, Neuhofer W, et al. (2016) LPS-induced NFκB enhanceosome requires TonEBP/NFAT5 without DNA binding. Sci Rep 6, 24921.
Kim JG, Nam-Goong IS, Yun CH, Jeong JK, Kim ES, Park JJ, Lee YC, Kim YI and Lee BJ (2006) TTF-1, a homeodomain-containing transcription factor, regulates feeding behavior in the rat hypothalamus. Biochem Biophys Res Commun 349, 969-975.
Hasler U, Leroy V, Jeon US, Bouley R, Dimitrov M, Kim JA, Brown D, Kwon HM, Martin PY and Féraille E (2008) NF-kappaB modulates aquaporin-2 transcription in renal collecting duct principal cells. J Biol Chem 283, 28095-28105.
Kuper C, Fraek ML, Muller HH, Beck FX and Neuhofer W (2012) Sepsis-induced urinary concentration defect is related to nitric oxide-dependent inactivation of TonEBP/NFAT5, which downregulates renal medullary solute transport proteins and aquaporin-2. Crit Care Med 40, 1887-1895.
Choi S, You SY, Kim DH, Choi SY, Kwon HM, Kim HS, Hwang D, Park YJ, Cho CS and Kim WU (2017) Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis. J Clin Invest 127, 954-969.
Jang PG, Namkoong C, Kang GM, Hur MW, Kim SW, Kim GH, Kang Y, Jeon MJ, Kim EH, Lee MS, et al. (2010) NF-kappaB activation in hypothalamic proopiomelanocortin neurons is essential in illness-and leptin-induced anorexia. J Biol Chem 285, 9706-9715.
Lee JH, Suh JH, Choi SY, Kang HJ, Lee HH, Ye BJ, Lee GR, Jung SW, Kim CJ, Lee-Kwon W, et al. (2019) Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis. Gut 68, 347-358.