2024-03-29T13:09:51Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00020817
2022-12-14T04:18:09Z
1016:1017
Theophylline suppresses interleukin-6 expression by inhibiting glucocorticoid receptor signaling in pre-adipocytes
Mitani, Takakazu
Takaya, Tomohide
Harada, Naoki
Katayama, Shigeru
Yamaji, Ryoichi
Nakamura, Soichiro
Ashida, Hitoshi
© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Adipocyte
CCAAT-Enhancer-binding proteins
Glucocorticoid receptor
Interleukin-6
Theophylline
Adipose tissues in obese individuals are characterized by a state of chronic low-grade inflammation. Pre-adipocytes and adipocytes in this state secrete pro-inflammatory adipokines, such as interleukin 6 (IL-6), which induce insulin resistance and hyperglycemia. Theophylline (1,3-dimethylxanthine) exerts anti-inflammatory effects, but its effects on pro-inflammatory adipokine secretion by pre-adipocytes and adipocytes have not been examined. In this study, we found that theophylline decreased IL-6 secretion by 3T3-L1 pre-adipocytes and mouse-derived primary pre-adipocytes. The synthetic glucocorticoid dexamethasone (DEX) induced IL-6 expression in 3T3-L1 pre-adipocytes, and this effect was suppressed by theophylline at the mRNA level. Knockdown of CCAAT/enhancer binding protein (C/EBP) δ inhibited DEX-induced IL-6 expression, and theophylline suppressed C/EBPδ expression. Furthermore, theophylline suppressed transcriptional activity of the glucocorticoid receptor (GR) through suppression of nuclear localization of GR. In vivo, glucocorticoid corticosterone treatment (100 μg/mL) increased fasting blood glucose and plasma IL-6 levels in C57BL/6 N mice. Theophylline administration (0.1% diet) reduced corticosterone-increased fasting blood glucose, plasma IL-6 levels, and Il6 gene expression in adipose tissues. These results show that theophylline administration attenuated glucocorticoid-induced hyperglycemia and IL-6 production by inhibiting GR activity. The present findings indicate the potential of theophylline as a candidate therapeutic agent to treat insulin resistance and hyperglycemia.
Article
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS.646:98-106(2018)
ELSEVIER SCIENCE INC
2018-05-15
eng
journal article
AM
http://hdl.handle.net/10091/00021575
https://soar-ir.repo.nii.ac.jp/records/20817
https://pubmed.ncbi.nlm.nih.gov/29625124/
29625124
https://doi.org/10.1016/j.abb.2018.04.001
10.1016/j.abb.2018.04.001
0003-9861
AA00547159
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
646
98
106
https://soar-ir.repo.nii.ac.jp/record/20817/files/2018_ArchBiochemBiophys_Mitani_SOAR.pdf
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2019-07-24