Glucocorticoids attenuate interleukin‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells

Bongartz, Hannes; Seiß, Elena A.; Bock, Jörg; Schaper, Fred

doi:10.1111/jnc.15305

Cited by 5 publications

(3 citation statements)

References 96 publications

(152 reference statements)

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“…We observed that IL6 also stimulated ERK1/2 phosphorylation in Neuro 2A cells (Figure 2E). These data revealed the potential of IL6 in stimulating neuronal activity and ERK1/2 phosphorylation, as previously reported 16,17 .…”

Section: Main Textsupporting

confidence: 89%

Evidence for a neuromuscular circuit involving hypothalamic Interleukin-6 signaling in the control of skeletal muscle metabolism

Katashima

Micheletti

Moura‐Assis

et al. 2021

Preprint

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Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control, including energy expenditure1, food consumption2, glucose homeostasis2, etc. Here we demonstrated that Interleukin-6 (IL6) activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mice skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1-2 axis is closely associated with firing-rate-related genes in the hypothalamus and with fatty acid oxidation- and mitochondrial-related genes in skeletal muscle of genetically diverse BXD mice strains and humans. Using surgical denervation, pharmacological approaches, and transgenic mice, we showed that the hypothalamic IL6/ERK1/2 pathway requires the a2-adrenergic pathway to modify the fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuitry is required to underpin AMPK/ACC signaling activation and fatty acid oxidation post-exercise. Once the selective downregulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle post-exercise. Altogether, these data demonstrated that IL6/ERK axis in VMH controls fatty acid metabolism in mice skeletal muscle.

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Section: Main Textsupporting

confidence: 89%

Evidence for a neuromuscular circuit involving hypothalamic Interleukin-6 signaling in the control of skeletal muscle metabolism

Katashima

Micheletti

Moura‐Assis

et al. 2021

Preprint

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“…These data indicate that the activation of downstream IL-6 signaling mechanisms within knee joint tissues and their associated DRG neurons may play essential roles in PTOA-associated cartilage degeneration and pain in male mice. Notably, IL-6 signaling through MAPKs, such as ERK, has been shown to induce neurite outgrowth in PC12 cells ( 55 ) and is also strongly implicated in the pathogenesis of pain ( 56 ).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner

et al. 2022

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Osteoarthritis (OA) and posttraumatic OA (PTOA) are caused by an imbalance in catabolic and anabolic processes in articular cartilage and proinflammatory changes throughout the joint, leading to joint degeneration and pain. We examined whether interleukin-6 (IL-6) signaling contributed to cartilage degradation and pain in PTOA. Genetic ablation of Il6 in male mice decreased PTOA-associated cartilage catabolism, innervation of the knee joint, and nociceptive signaling without improving PTOA-associated subchondral bone sclerosis or chondrocyte apoptosis. These effects were not observed in female Il6 −/− mice. Compared with wild-type mice, the activation of the IL-6 downstream mediators STAT3 and ERK was reduced in the knees and dorsal root ganglia (DRG) of male Il6 −/− mice after knee injury. Janus kinases (JAKs) were critical for STAT and ERK signaling in cartilage catabolism and DRG pain signaling in tissue explants. Whereas STAT3 signaling was important for cartilage catabolism, ERK signaling mediated neurite outgrowth and the activation of nociceptive neurons. These data demonstrate that IL-6 mediates both cartilage degradation and pain associated with PTOA in a sex-specific manner and identify tissue-specific contributions of downstream effectors of IL-6 signaling, which are potential therapeutic targets for disease-modifying OA drugs.

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“…Early growth response (EGR) family and regulated by melatonin and are involved in several cellular responses, which are known to be related to circadian rhythm [ 14 – 17 ]. EGR1 is one of the early downstream nuclear targets for changes in the extracellular stimulation [ 18 , 19 ], which could be rapidly induced by cytokines, hormones, and stress signals [ 20 ]. EGR1 could suppress the transcription of adipose triglyceride lipase and adipogenesis [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway

Wan,

Wang,

Khan

et al. 2024

Cell Death Discov.

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The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

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Glucocorticoids attenuate interleukin‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 5 publications

References 96 publications

Evidence for a neuromuscular circuit involving hypothalamic Interleukin-6 signaling in the control of skeletal muscle metabolism

Evidence for a neuromuscular circuit involving hypothalamic Interleukin-6 signaling in the control of skeletal muscle metabolism

Interleukin-6 signaling mediates cartilage degradation and pain in posttraumatic osteoarthritis in a sex-specific manner

Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway

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