Inflammation最新文献

{"title":"UVB Induces Sympathetic Nervous System Activation and Norepinephrine Secretion to Regulate The Skin Color of Mice Through the β2-AR/AP-1 Pathway in Epidermal Keratinocytes.","authors":"Qirui Deng, Xinyan Liu, Xiujuan Wen, Hao Huang, Hongfeng Tang","doi":"10.1007/s10753-024-02221-0","DOIUrl":"https://doi.org/10.1007/s10753-024-02221-0","url":null,"abstract":"<p><p>The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA-seq Reveals Increased and Activated Post-Capillary Venule Endothelial Cells in Erythrodermic Psoriasis.","authors":"Xiaoyan Wu, Yun Luo, Leying Liu, Changxu Han, Yuhua Liu, Zhenying Zhang","doi":"10.1007/s10753-024-02216-x","DOIUrl":"https://doi.org/10.1007/s10753-024-02216-x","url":null,"abstract":"<p><p>Erythrodermic psoriasis (EP) is a life-threatening variant of psoriasis. In this study, we contrasted the vascular endothelial cells (ECs) in EP lesions against those in psoriasis vulgaris and healthy controls. Utilizing single-cell RNA sequencing, immunofluorescence, and flow cytometry on human and mouse samples, we observed a marked increase and activation of EP ECs, which upregulated genes relative to angiogenesis, leukocyte adhesion and antigen presentation. This was particularly evident in the subpopulation post-capillary venules (PCV), especially the cluster from EP. Cell-cell communication studies revealed intensified interactions between PCV and leukocytes, mediated by SELE and ICAM1, predominantly in EP. Trajectory analysis suggested differentiation direction of venules-PCV-CAP. 1 with a concomitant reduction in NF2R2 expression. Elevated and activated PCVs were found in EP patient biopsies and mouse models. These findings underscore the significance of PCV in EP pathogenesis, presenting new therapeutic avenues for this debilitating disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.","authors":"Yitian Lai, Ranran Qiu, Jingying Zhou, Ling Ren, Yizhuo Qu, Guoshan Zhang","doi":"10.1007/s10753-024-02233-w","DOIUrl":"https://doi.org/10.1007/s10753-024-02233-w","url":null,"abstract":"<p><p>Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the \"gut-lung axis\" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The \"gut-lung axis\" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the \"gut-lung axis\" theory.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Anti-inflammatory Potential of JN-KI3: The Therapeutic Role of PI3Kγ-Selective Inhibitors in Asthma Treatment.","authors":"Lei Jia, Mengyun Ma, Wendian Xiong, Jingyu Zhu, Yanfei Cai, Yun Chen, Jian Jin, Mingzhu Gao","doi":"10.1007/s10753-024-02180-6","DOIUrl":"https://doi.org/10.1007/s10753-024-02180-6","url":null,"abstract":"<p><p>Asthma is a chronic airway inflammatory disease of the airways characterized by the involvement of numerous inflammatory cells and factors. Therefore, targeting airway inflammation is one of the crucial strategies for developing novel drugs in the treatment of asthma. Phosphoinositide 3-kinase gamma (PI3Kγ) has been demonstrated to have a significant impact on inflammation and immune responses, thus emerging as a promising therapeutic target for airway inflammatory disease, including asthma. There are few studies reporting on the therapeutic effects of PI3Kγ-selective inhibitors in asthma disease. In this study, we investigated the anti-inflammatory and therapeutic effects of PI3Kγ-selective inhibitor JN-KI3 for treating asthma by utilizing both in vivo and in vitro approaches, thereby proving that PI3Kγ-selective inhibitors could be valuable in the treatment of asthma. In RAW264.7 macrophages, JN-KI3 effectively suppressed C5a-induced Akt phosphorylation in a concentration-dependent manner, with no discernible toxicity observed in RAW264.7 cells. Furthermore, JN-KI3 can inhibit the PI3K/Akt signaling pathway in lipopolysaccharide-induced RAW264.7 cells, leading to the suppression of transcription and expression of the classical inflammatory cytokines in a concentration-dependent manner. Finally, an ovalbumin-induced murine asthma model was constructed to evaluate the initial therapeutic effect of JN-KI3 for treating asthma. Oral administration of JN-KI3 inhibited the infiltration of inflammatory cells and the expression of T-helper type 2 cytokines in bronchoalveolar lavage fluid, which was associated with the suppression of the PI3K signaling pathway. Lung tissue and immunohistochemical studies demonstrated that JN-KI3 inhibited the accumulation of inflammatory cells around the bronchus and blood vessels, as well as the secretion of mucus and excessive deposition of collagen around the airway. In addition, it reduced the infiltration of white blood cells into the lungs. In summary, JN-KI3 shows promise as a candidate for the treatment of asthma. Our study also suggests that the inhibitory effects of PI3Kγ on inflammation could offer an additional therapeutic strategy for pulmonary inflammatory diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated IL-17A-Secreting Regulatory T Cells in Sinonasal Tissues of Chronic Rhinosinusitis with Nasal Polyps.","authors":"Gwanghui Ryu, Jun-Sang Bae, Shin Hyuk Yoo, Eun Hee Kim, Ji-Hun Mo","doi":"10.1007/s10753-024-02227-8","DOIUrl":"https://doi.org/10.1007/s10753-024-02227-8","url":null,"abstract":"<p><p>During nasal polyp (NP) development, activated T cells differentiate into T helper (Th) 1, Th2, and Th17 cells. Additionally, regulatory T cells (Tregs) that have an immune suppressive function are involved in the pathophysiology of chronic rhinosinusitis (CRS) with NP (CRSwNP). Tregs can act as effector cells that produce inflammatory cytokines, such as interleukin (IL)-17A. We sought to identify the cellular expression of IL-17A and Treg markers in sinonasal tissue from CRSwNP patients and to investigate whether Tregs are involved in IL-17A secretion. The uncinate process (UP) and NP tissues were harvested from patients with CRSwNP, CRS without NP (CRSsNP), and normal controls. Expression of IL-17A and Foxp3 in each group was observed with immunohistochemistry and immunofluorescence. Expression of IL-17A in Treg was evaluated by flow cytometry of single cells isolated from sinonasal tissues. UP tissue from controls (n = 17), UP from CRSsNP (n = 24), and UP (n = 19) and NP (n = 29) from CRSwNP were obtained. The percentage of Foxp3⁺ cells was higher in CRS tissues compared with normal controls. IL-17A⁺ cells were most increased in NP tissues from CRSwNP patients. Expression of IL-17A in some Foxp3⁺ cells was observed in double immunofluorescence. Foxp3⁺ cells, IL-17A⁺ cells, and Foxp3⁺IL-17A⁺ cells were increased in the UP and NP tissues from CRSwNP patients. CD45RA^-Foxp3⁺ cells were increased in CRSwNP, and IL-17A⁺ cells were observed most frequently in CD4⁺CD45RA^-Foxp3⁺ cells from NP tissues. These findings show that CD4⁺CD45RA^-Foxp3⁺ Tregs are involved in NP pathogenesis by producing IL-17A.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NG-497 Alleviates Microglia-Mediated Neuroinflammation in a MTNR1A-Dependent Manner.","authors":"Qi Li, Pinyi Liu, Xuan Zhu, Chao Zhou, Yujie Hu, Shiying Cao, Huiya Li, Xinxin Zou, Shenghan Gao, Xiang Cao, Xinyu Bao, Yun Xu, Jingwei Li","doi":"10.1007/s10753-024-02218-9","DOIUrl":"https://doi.org/10.1007/s10753-024-02218-9","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation plays a crucial role in multiple neurological diseases. We have previously found that Atglistatin, the mouse Adipose Triglyceride Lipase (ATGL) inhibitor, could promote lipid droplets (LDs) accumulation and suppress LPS-induced neuroinflammation in mouse microglia. However, Atglistatin was species-selective, which limited its use in clinical settings. Here, we found that NG-497, a previously identified human ATGL inhibitor, significantly increased LDs accumulation and inhibited LPS-induced pro-inflammatory responses in human microglia. Moreover, NG-497 also protected human neurons against neurotoxic cytokines in a humanized in vitro model of neuroinflammation. However, the anti-inflammatory capacity of NG-497 was independent of its effect on ATGL. Instead, we revealed that NG-497 alleviated microglia-mediated neuroinflammation through elevating the protein level of melatonin receptor 1A (MTNR1A). Therefore, in this study, we uncovered a novel MTNR1A-targeting compound, which exhibited anti-inflammatory and neuroprotective effect, highlighting its potential in the treatment of neuroinflammation. Moreover, the MTNRs agonist, Ramelteon, exerts comparable anti-inflammation effects with NG-497.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F2RL1 Inhibition Alleviates Lipotoxicity-Induced Kidney Injury Through the Hippo Pathway in Diabetic Kidney Disease.","authors":"Hui Wang, Wei Wang, Yao Jiang, Siyuan Cui, Yulin Kong, Yong Q Chen, Shenglong Zhu","doi":"10.1007/s10753-024-02215-y","DOIUrl":"https://doi.org/10.1007/s10753-024-02215-y","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD), which is emerging as a pervasive global health concern and a considerable economic burden, is characterized by a detrimental effect on renal function and structure. Recent research indicates that the progression of DKD is facilitated by lipotoxic injury to tubular epithelial cells (TECs). However, the specific mechanisms that contribute to this cellular damage have yet to be fully elucidated. Our results revealed a significant upregulation of F2RL1 in vivo and in vitro models, which was positively correlated with the expression of inflammatory factors. Knockdown of F2RL1 significantly reduced inflammatory response in palmitate-stimulated HK-2 cells. Mechanistically, F2RL1 might exacerbate lipotoxicity-induced DKD through the modulation of the Hippo signaling pathway. Collectively, these findings suggest that modulating F2RL1 expression may be a strategic approach to mitigate the inflammatory damage to RTECs associated with DKD, potentially through its involvement in the Hippo signaling pathway. Given these findings, F2RL1 merits consideration as a candidate therapeutic target for DKD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.","authors":"Mitra Gultom, Lin Lin, Camilla Blunk Brandt, Anastasia Milusev, Alain Despont, Jane Shaw, Yvonne Döring, Yonglun Luo, Robert Rieben","doi":"10.1007/s10753-024-02208-x","DOIUrl":"https://doi.org/10.1007/s10753-024-02208-x","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-α. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA Tug1 Regulates Post-Stroke Microglial Pyroptosis via PINK1/Parkin-Mediated Mitophagy.","authors":"Meiling Yao, Xiaobei Wang, Hao Lin, Hui Shu, Zongtang Xu, Ling Tang, Wenyuan Guo, Pingyi Xu","doi":"10.1007/s10753-024-02219-8","DOIUrl":"https://doi.org/10.1007/s10753-024-02219-8","url":null,"abstract":"<p><p>Microglia, the central nervous system's primary immune cells, play a key role in the progression of cerebral ischemic stroke, particularly through their involvement in pyroptosis. The long non-coding RNA taurine up-regulated gene 1 (Tug1) is elevated during ischemic stroke and is critical in driving post-stroke neuroinflammation. However, the underlying molecular mechanisms remain unclear. This study explores the biological role of Tug1 and its potential mechanisms in regulating pyroptosis in microglia. We utilized an in vivo photothrombosis (PT) mice model and an in vitro oxygen-glucose deprivation and reperfusion (OGD/R) BV2 cell model to explore the mechanisms underlying ischemic stroke. Initially, we assessed the expression levels of Tug1 in the OGD/R model in vitro and the PT model in vivo. Subsequently, we investigated the impact of Tug1 on microglial pyroptosis by knocking down Tug1, silencing the PTEN-induced putative kinase 1 (Pink1) expression, and employing the mitophagy inhibitor mdivi-1. Tug1 exacerbated microglial pyroptosis by inhibiting mitophagy in both in vivo and in vitro models. The increase in mitophagy observed following Tug1 knockdown was reversed by either silencing Pink1 expression or using the mitophagy inhibitor mdivi-1. This reversal resulted in exacerbated pyroptosis and worsened neurological damage. Further mechanistic studies revealed that Tug1 knockdown significantly reduced microglial pyroptosis and alleviated neuronal damage by enhancing PINK1/Parkin-mediated mitophagy. For the first time, this study reveals that Tug1 promotes hypoxia-induced microglial pyroptosis by inhibiting PINK1/Parkin-mediated mitophagy, potentially providing a promising therapeutic target for ischemic inflammatory injury.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p62 Binding to Protein Kinase C Regulates HIV-1 gp120 V3 Loop Induced Microglial Inflammation.","authors":"Huili Wang, Qin Zuo, Xinyi Li, Yuanyuan Liu, Limeng Gan, Linlin Wang, Yin Rao, Rui Pan, Jun Dong","doi":"10.1007/s10753-024-02229-6","DOIUrl":"https://doi.org/10.1007/s10753-024-02229-6","url":null,"abstract":"<p><p>The main pathogenic mechanism of HIV-associated neurocognitive disorders (HAND) is neuronal apoptosis induced by inflammatory mediators, in which microglial inflammation plays a crucial role. However, the exact pathogenic mechanism remains unclear. Previous studies have shown that the HIV-1 gp120 V3 loop can trigger inflammation in CHME-5 microglia. p62 is a post-translational modified multidomain protein that is involved in the regulation of autophagy and is closely related to neuroinflammation. In this study, we found that p62 knockout down-regulated the expression of MCP-1, IL-6 and COX-2, and improved the inflammation of HIV-1 gp120 V3 loop induced microglia, while overexpression of p62 up-regulated the expression of MCP-1, IL-6 and COX-2, and promoted the inflammation of microglia. In addition, protein kinase C (PKC) knockout down-regulated the expression of MCP-1, IL-6 and COX-2 and inhibited the activation of IKK/ NF-κ B pathway, while tumor necrosis factor receptor-associated factor 6 (TRAF6) knockout had no significant effect on the expression of MCP-1, IL-6 and COX-2. Co-immunoprecipitation showed that p62 was bound and interacted with PKC. Inhibition of IKK/ NF-κ B pathway can down-regulate the expression of MCP-1, IL-6 and COX-2, and improve the inflammatory response of microglia. Our research further found that inhibition of IKK/ NF-κ B can decrease the expression of Caspase-3 and reduce the apoptosis of neurons in the co-culture of CHME-5 microglia and primary mouse neurons. The results of this study suggest that HIV-1 gp120 V3 loop induced CHME-5 microglial inflammation may be activated by the direct binding of p62 and PKC through the IKK/ NF-κ B signaling pathway, and these findings provide an important reference for the prevention and treatment of HAND.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}