CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia

Hu, Zhongsheng; Deng, Nan; Liu, Kaili; Zhou, Nan; Sun, Yue; Zeng, Wenwen

doi:10.1016/j.celrep.2020.107657

Cited by 102 publications

(67 citation statements)

References 67 publications

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“…Future work directed at delineating the specific roles of specific class I isoforms would be beneficial since there are a variety of pan- and isoform-specific inhibitors in clinical trial. Importantly, there are other pain mediators, such as STAT3 ( Liu et al, 2013 ; Zhang et al, 2017 ; Hu et al, 2020 ), that are also activated by EGFR ( Han and Lo, 2012 ). The extent to which these targets contribute to EGFR-mediated hypersensitivity remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

et al. 2021

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Chronic pain has been widely recognized as a major public health problem that impacts multiple aspects of patient quality of life. Unfortunately, chronic pain is often resistant to conventional analgesics, which are further limited by their various side effects. New therapeutic strategies and targets are needed to better serve the millions of people suffering from this devastating disease. To this end, recent clinical and preclinical studies have implicated the epidermal growth factor receptor signaling pathway in chronic pain states. EGFR is one of four members of the ErbB family of receptor tyrosine kinases that have key roles in development and the progression of many cancers. EGFR functions by activating many intracellular signaling pathways following binding of various ligands to the receptor. Several of these signaling pathways, such as phosphatidylinositol 3-kinase, are known mediators of pain. EGFR inhibitors are known for their use as cancer therapeutics but given recent evidence in pilot clinical and preclinical investigations, may have clinical use for treating chronic pain. Here, we review the clinical and preclinical evidence implicating EGFR in pathological pain states and provide an overview of EGFR signaling highlighting how EGFR and its ligands drive pain hypersensitivity and interact with important pain pathways such as the opioid system.

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Section: Discussionmentioning

confidence: 99%

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

et al. 2021

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“…COVID‐19 may cause cytokine storm, which is defined as increasing plasma concentrations of various cytokines triggered by an uncontrolled immune response, increased proliferation of immune system cells and overproduction of signal molecules (Hu et al., 2020 ; Mulchandani et al., 2021 ). The release of cytokines affects unfavourably all organ systems, particularly the lung tissue (Hu et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The effect of interleukin‐6 level at the time of hospitalisation on erectile functions in hospitalised patients with COVID‐19

et al. 2021

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We evaluated the relationship between erectile dysfunction (ED) and IL‐6 levels in males with COVID‐19. The study included 80 male patients aged 30–45 years who were hospitalised due to COVID‐19. The International Index of Erectile Function (IIEF‐5) questionnaire was used to assess erectile function. The IIEF‐5 questionnaire was re‐administered at a 3‐month control visit after discharge, and the change score from baseline was recorded. The patients were divided into three groups according to the IIEF‐5 score at 3 months as Group 1 (severe ED), Group 2 (moderate ED) and Group 3 (no ED), and into two groups according to IL‐6 level at the time of admission as Group A (IL‐6 ≤ 50 ng/ml) and Group B (IL‐6 > 50 ng/ml). The change in the IIEF‐5 score (p < .001) was significantly greater in Group B than in Group A. There was also significant difference in IL‐6 between Group 1 and Group 2 (p = .008). The correlation analysis revealed a moderate correlation between IL‐6 level and the change in IIEF‐5 score and D‐dimer level (r:0.529, p < .001) and a weak correlation between IL‐6 level and FSH (r:0.309, p = .005). The present study suggests that elevated IL‐6 levels in male patients hospitalised due to COVID‐19 might be related to the risk of developing ED.

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“…STAT3 is an essential transcription factor for survival, growth, protection, and metabolic regulation (Murase et al, 2012, Bareyre et al, 2011, Feng et al, 2019, Desai and Harris, 2015. At the behavioral level, STAT3 has a direct impact on multiple animal behaviors, such as running, food-intake, and pain (Mesaros et al, 2008, Herrmann et al, 2008, Fernandes et al, 2015, Buettner et al, 2006, Desai and Harris, 2015, Hu et al, 2020, Guo et al, 2018. Animals struggling for survival generally show locomotive and food-intake behaviors.…”

Section: Introductionmentioning

confidence: 99%

Ablation of STAT3 in Purkinje Cells Reorganizes Cerebellar Synaptic Plasticity in Long-Term Fear Memory Network

Han

Kwon

Kim

et al. 2020

Preprint

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Emotional memory processing, such as fear memory, engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network is largely unknown. Here, we illustrate a novel mechanism by which synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Firstly, we generated PC-specific STAT3 knockout (STAT3PKO) mice. Transcriptome analyses revealed that STAT3 deletion results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber to PC synapses was larger in STAT3PKO mice than in wild-type littermates. Conditioning at the parallel fiber induced long-term depression of parallel fiber-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in wild-type littermates. Interestingly, STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory processing.

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CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia

Cited by 102 publications

References 67 publications

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

Modulation of Pathological Pain by Epidermal Growth Factor Receptor

The effect of interleukin‐6 level at the time of hospitalisation on erectile functions in hospitalised patients with COVID‐19

Ablation of STAT3 in Purkinje Cells Reorganizes Cerebellar Synaptic Plasticity in Long-Term Fear Memory Network

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