Integrated analysis reveals Atf3 promotes neuropathic pain via orchestrating JunB mediated release of inflammatory cytokines in DRG macrophage

Deng, Yingdong; Tang, Simin; Cheng, J.; Zhang, Xiangsheng; Jing, Dengwei; Lin, Zhifeng; Zhou, Jun

doi:10.1016/j.lfs.2023.121939

Cited by 2 publications

(2 citation statements)

References 64 publications

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“…JunB was identified as a central regulator of the immunosuppressive, non-inflamed TME, as it negatively correlated with antigen presentation by MHC molecules, immune cell recruitment, anti-cancer immune response, and immune checkpoint inhibitors, thereby contributing to an unfavorable prognosis of tumor patients. Secondly, JunB mediated the release of inflammatory factors in dorsal root ganglion macrophages, promoting neuropathic pain [63]. In addition, microglial JunB inhibited inflammation and apoptosis during ischemia/reperfusion in brain injury [64].…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in the Metastatic Microenvironment: JunB-Expressing Microglia Cells as Potential Drivers of Melanoma Brain Metastasis Progression

Adir,

Sagi-Assif,

Meshel

et al. 2023

Cancers

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Reciprocal signaling between melanoma brain metastatic (MBM) cells and microglia reprograms the phenotype of both interaction partners, including upregulation of the transcription factor JunB in microglia. Here, we aimed to elucidate the impact of microglial JunB upregulation on MBM progression. For molecular profiling, we employed RNA-seq and reverse-phase protein array (RPPA). To test microglial JunB functions, we generated microglia variants stably overexpressing JunB (JunBhi) or with downregulated levels of JunB (JunBlo). Melanoma-derived factors, namely leukemia inhibitory factor (LIF), controlled JunB upregulation through Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling. The expression levels of JunB in melanoma-associated microglia were heterogeneous. Flow cytometry analysis revealed the existence of basal-level JunB-expressing microglia alongside microglia highly expressing JunB. Proteomic profiling revealed a differential protein expression in JunBhi and JunBlo cells, namely the expression of microglia activation markers Iba-1 and CD150, and the immunosuppressive molecules SOCS3 and PD-L1. Functionally, JunBhi microglia displayed decreased migratory capacity and phagocytic activity. JunBlo microglia reduced melanoma proliferation and migration, while JunBhi microglia preserved the ability of melanoma cells to proliferate in three-dimensional co-cultures, that was abrogated by targeting leukemia inhibitory factor receptor (LIFR) in control microglia–melanoma spheroids. Altogether, these data highlight a melanoma-mediated heterogenous effect on microglial JunB expression, dictating the nature of their functional involvement in MBM progression. Targeting microglia highly expressing JunB may potentially be utilized for MBM theranostics.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity in the Metastatic Microenvironment: JunB-Expressing Microglia Cells as Potential Drivers of Melanoma Brain Metastasis Progression

Adir,

Sagi-Assif,

Meshel

et al. 2023

Cancers

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“…It is generally chronic and is caused by lesions within the somatosensory system, which bidirectionally communicates with the immune system [8][9][10][11]. Single-cell RNA sequencing has revealed upregulated immune system-related genes in the dorsal root ganglia (DRG), sciatic nerves, and spinal cord in a neuropathic pain model [12][13][14]. Consequently, regulating inflammatory responses under pathological conditions offers potential pain alleviation, and inflammation-modulating medications are promising therapeutic agents for pain management [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Role of Resolvins in Inflammatory and Neuropathic Pain

Park,

Roh,

Pan

et al. 2023

Pharmaceuticals

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Chronic pain is an unpleasant experience associated with actual or potential tissue damage. Inflammatory pain alerts the body to inflammation and promotes healing; however, unresolved inflammation can lead to chronic pain. Conversely, neuropathic pain, due to somatosensory damage, can be a disease in itself. However, inflammation plays a considerable role in the progression of both types of pain. Resolvins, derived from omega-3 fatty acids, actively suppress pro-inflammatory mediators and aid in the resolution of inflammation. Resolvins alleviate various inflammatory and neuropathic pain models by reducing hypersensitivity and regulating inflammatory cytokines and glial activation in the spinal cord and dorsal root ganglia. Thus, resolvins are a promising alternative for pain management with the potential to reduce the side effects associated with conventional medications. Continued research is crucial to unlock the therapeutic potential of resolvins and integrate them into effective clinical pain management strategies. This review aimed to evaluate the literature surrounding the resolvins in inflammatory and neuropathic pain.

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Integrated analysis reveals Atf3 promotes neuropathic pain via orchestrating JunB mediated release of inflammatory cytokines in DRG macrophage

Cited by 2 publications

References 64 publications

Heterogeneity in the Metastatic Microenvironment: JunB-Expressing Microglia Cells as Potential Drivers of Melanoma Brain Metastasis Progression

Heterogeneity in the Metastatic Microenvironment: JunB-Expressing Microglia Cells as Potential Drivers of Melanoma Brain Metastasis Progression

Role of Resolvins in Inflammatory and Neuropathic Pain

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