β2‐adrenergic stimulation induces interleukin‐6 by increasing Arid5a, a stabilizer of mRNA, through cAMP/PKA/CREB pathway in cardiac fibroblasts
| العنوان: | β2‐adrenergic stimulation induces interleukin‐6 by increasing Arid5a, a stabilizer of mRNA, through cAMP/PKA/CREB pathway in cardiac fibroblasts |
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| المؤلفون: | Atsuki Imaeda, Masanori Obana, Kotaro Matsumoto, Yasushi Fujio, Makiko Maeda, Shota Tanaka |
| المصدر: | Pharmacology Research & Perspectives Pharmacology Research & Perspectives, Vol 8, Iss 2, Pp n/a-n/a (2020) |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Stimulation, RM1-950, CREB, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, medicine, Cyclic AMP, Animals, RNA, Messenger, General Pharmacology, Toxicology and Pharmaceutics, Interleukin 6, Cyclic AMP Response Element-Binding Protein, Mice, Knockout, Messenger RNA, biology, Chemistry, Interleukin-6, Binding protein, Myocardium, Isoproterenol, Transcription Factor RelA, Interleukin, Original Articles, Adrenergic beta-Agonists, Fibroblasts, β adrenergic receptor, Cyclic AMP-Dependent Protein Kinases, DNA-Binding Proteins, Mice, Inbred C57BL, Endocrinology, Neurology, interleukin‐6, 030220 oncology & carcinogenesis, Knockout mouse, biology.protein, Original Article, Female, Therapeutics. Pharmacology, Receptors, Adrenergic, beta-2, Signal Transduction, Transcription Factors |
| الوصف: | Background and Purpose In cardiovascular diseases, cardiac fibroblasts (CFs) participate in the myocardial inflammation by producing pro‐inflammatory cytokines, worsening the prognosis. β2‐adrenergic receptor (AR) and β3AR are expressed in CFs, and β‐adrenergic stimulation promotes CFs to produce pro‐inflammatory cytokines. However, the mechanism of the expression of pro‐inflammatory cytokines in response to β‐adrenergic stimulation remains to be fully elucidated. Experimental Approach CFs were isolated from adult wild‐type or AT‐rich interactive domain‐containing protein 5A (Arid5a) knockout mice. The expression of mRNA was measured by real‐time RT‐PCR. Interleukin (IL)‐6 protein was measured by ELISA. The activity of nuclear factor‐κB (NF‐κB) and cyclic AMP (cAMP) response element binding protein (CREB) was assessed by ELISA‐like assay or Western blotting. Key Results The β‐adrenergic stimulation remarkably induced IL‐6 mRNA and protein through β2AR in CFs. The activation of adenylate cyclase and the enhancement of intracellular cAMP resulted in the upregulation of IL‐6 mRNA expression. The induction of IL‐6 transcript by β2AR signaling was independent of NF‐κB. Concomitant with IL‐6, the expression of Arid5a, an IL‐6 mRNA stabilizing factor, was enhanced by β2‐adrenergic stimulation and by cAMP increase. Importantly, β2AR signaling‐mediated IL‐6 induction was suppressed in Arid5a knockout CFs. Finally, β2AR stimulation phosphorylated CREB via PKA pathway, and the activation of CREB was essential for the induction of Arid5a and IL‐6 mRNA. Conclusion and Implications β2‐adrenergic stimulation post‐transcriptionally upregulates the expression of IL‐6 by the induction of Arid5a through cAMP/PKA/CREB pathway in adult CFs. β2AR/Arid5a/IL‐6 axis could be a therapeutic target against cardiac inflammation. |
| اللغة: | English |
| تدمد: | 2052-1707 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::93f9216714d65d9cdf9f10b68923845f http://europepmc.org/articles/PMC7164407 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....93f9216714d65d9cdf9f10b68923845f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20521707 |
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