The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becomi...The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.展开更多
Objective: To explore the underlying molecular mechanisms of cellular response to the challenge by 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of PC12 cells, an in vitro cell model for Parkinson’s disease, a...Objective: To explore the underlying molecular mechanisms of cellular response to the challenge by 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of PC12 cells, an in vitro cell model for Parkinson’s disease, and the effect of NF-κB activation on the protection of Parkinson’s disease by Isoflavone (I). Methods: PC12 cells were used to establish the cell model of Parkinson’s disease, and are divided into five groups: control group;MPP+ group;I (Isoflavone) + MPP+ group;I group;SN-50 + MPP+ group. The content of NF-κB in PC12 cells was determined by immunocytochemistry;The viability of PC12 cells after treated with cell-permeable NF-κB inhibitor SN-50 and cell viability were measured by MTT assay;the expression levels of NF-κB p65 in cytoplasm and nuclear fractions were evaluated by western blot analysis;the mRNA expression of NF-κB p65 was analyzed by in situ hybridization (ISH). Results: Compared with the control group, the protein of NF-κB p65 both in cytoplasm and in nuclei was significantly higher than in I + MPP+ and MPP+ groups;similarly, the mRNA expression level of NF-κB p65 gene was also significantly higher;moreover, the protein expression of NF-κB p65 was much lower in I group (P + group, the protein of NF-κB p65 was significantly lower in I + MPP+ group, the mRNA expression level of NF-κB p65 gene was also significantly lower, and the protein expression level of NF-κB p65 was much lower in I + MPP+ group (P + group (P > 0.05). Conclusion: NF-κB activation is essential to MPP+-induced apoptosis in PC12 cells;but Isoflavone can inhibit the cell damage to some extent to execute its protective function, which may be involved in nigral neurodegeneration in patients with Parkinson’s disease.展开更多
Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, ...Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, growth factors, and bacterial and viral products. The aim of this study is to demonstrate NF-κB expression in the mouse cochlea and its enhancement in response to lipopolysaccharides(LPS) and kanamycin(KA) treatment. Methods KA treatment consisted of subcutaneous KA injections at 700 mg/kg twice a day with an eight-hour interval between the two injections for 3 or 7 days. For animals in the LPS treatment group, a single dose of 0.3 mg LPS dissolved in 0.2 ml sterile saline were injected into both bullae through the tympanic membrane and kept there for 3 hours. Animals in the control group received subcutaneous saline injection for 7 days. Following immmunohistochemichal processing with rabbit polyclonal anti-NF-κB p65 antibodies, cryosections of the cochlea were examined for expression of NF-κB p65 in various structures in the cochlea. Results NF-κB p65 expression, identified by presence of brown reaction products characteristic of DAB immunohistochemistry, was visible in the spiral ligament, spiral prominence, tectorial membrane(TM), spiral ganglion and nerve fibers. Relatively weak NF-κB p65 expression was also visualized in the organ of Corti. Within the organ of Corti, the inner hair cells(IHC), outer hair cells(OHC), inner pillar cells(IP), outer pillar cells (OP), Deiter’s cells(DC), and Boettcher’s cells exhibited stronger staining than the inner sulcus cells, Hensen’s cells(HC) and Claudius’cells. No NF-κB p65 expression was seen in the nucleus of the IHC and OHC. NF-κB p65 expression was increased in animals exposed to LPS or KA, demonstrating significant differences in the staining between control animals and LPS/KA-treated animals. NF-κB p65 expression was not significantly different between LPS treated and KA treated animals or between 3 and 7 days in KA-treated animals. Conclusion LPS and KA exposure increases expression of NF-κB p65 in the mouse cochlea.展开更多
Activation of nuclear factor kappa B （NF-κB） is a hallmark of various central nervous system （CNS） pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, p...Activation of nuclear factor kappa B （NF-κB） is a hallmark of various central nervous system （CNS） pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-~B in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans- dominant negative mutant of its upstream regulator IκBa, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro- gram in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.展开更多
To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adju...To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B （NF-KB） were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines （interferon-y, IL-12, IL-1β and TNF-α） were observed.RESULTS： The activity of p38 MAPK and NF-~：B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~：B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.展开更多
背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄...背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄芩苷及雷公藤甲素等中药单体治疗脊髓损伤后神经炎症的研究进展进行系统的阐述与归纳。方法:以“脊髓损伤,炎症,抗炎,中药单体,单体化合物,NF-κB信号通路,黄酮,糖苷,酚类,酯类,生物碱”为检索词在中国知网数据库中进行检索;以“Spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids”为检索词在PubMed数据库中进行检索,最终共纳入67篇文献进行综述分析。结果与结论:①核转录因子κB信号通路在神经系统中的作用复杂多样,能够调控中性粒细胞、小胶质细胞、星形胶质细胞和巨噬细胞等,介导损伤后炎症的发生与发展;②中药单体如汉黄芩苷对核转录因子κB抑制蛋白的降解、红花黄素对核转录因子κB信号通路磷酸化过程的抑制、山奈酚对核转录因子κB信号通路p65核易位的抑制等作用可以降低炎症反应对机体造成的影响,从而促进神经功能恢复;③核转录因子κB信号通路在损伤早期能够促进炎症反应和免疫细胞迁移活化,在损伤中后期能够促进损伤部位的修复和纤维化的发生等,适当的激活核转录因子κB信号通路具有促进炎症因子的释放、提高细胞的抗氧化能力及促进免疫细胞的活化等能力,但过度激活的核转录因子κB信号通路则容易导致慢性炎症的发生和持续、细胞凋亡受到抑制等;④未来的研究可以进一步探索如何准确调控核转录因子κB信号通路的活化水平、如何实现对神经系统炎症和损伤的精准干预展开,也可围绕中药单体的制备及中药单体对信号通路的作用机制展开,以期为神经系统疾病的康复和功能恢复提供更有效的治疗策略。展开更多
Objective: To investigate the expression relationship between nuclear transcription factor kappa B1 (NFκB1) and long non-coding RNA PACER (LncRNA-PACER) in peripheral blood mononuclear cells (PBMCs) of patients with ...Objective: To investigate the expression relationship between nuclear transcription factor kappa B1 (NFκB1) and long non-coding RNA PACER (LncRNA-PACER) in peripheral blood mononuclear cells (PBMCs) of patients with pulmonary tuberculosis. Methods: From February 2018 to March 2019, 40 patients with pulmonary tuberculosis (tuberculosis group) and 40 healthy persons (control group) were collected, the levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA);the expressions of LncRNA-PACER and NFκB1 mRNAs in PBMCs were detected by real-time fluorescence quantitative PCR;Western blot was used to detect the expressions of NFκB1 and COX 2 in PBMCs;Pearson method was used to analyze the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis, and the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis were analyzed. Results: Compared with the control group, the expressions of TNF-α, IL-6 and IL-8 in the serum of patients with pulmonary tuberculosis was significantly increased (P<0.05), and the expressions of LncRNA-PACER, NFκB1 mRNAs, proteins and COX-2 protein in PBMCs were significantly increased (P<0.05). The expressions of LncRNA-PACER and NFκB1 proteins in PBMCs were related to the number of pulmonary lesions and pulmonary cavity (P<0.05), and there was a positive correlation between the expression of LncRNA-PACER and the expression of NFκB1 mRNA in PBMCs of patients with pulmonary tuberculosis (r = 0.873, P<0.05). Conclusions: The expressions of NFκB1 and LncRNA-PACER in PBMCs of patients with pulmonary tuberculosis are significantly increased, they are positively correlated and both of them are related to the occurrence and development of pulmonary tuberculosis.展开更多
文摘The role of Toll-like receptor 4 (TLR4) and nuclear factor κB p65 (NF-κB p65) proteins in the pathogenesis of otitis media is explored. In recent years, the incidence of otitis media has been rising globally, becoming a significant threat to human health. More and more studies have found that Toll-like receptor 4 (TLR4), as a member of the Toll-like receptor family, can promote the generation of inflammatory factors and is closely related to the body’s immune response and inflammatory response. Nuclear factor-κB p65 (NF-κB p65) is a nuclear transcription factor that can interact with various cytokines, growth factors, and apoptotic factors, participating in processes such as oxidative stress, apoptosis, and inflammation in the body [1]. This article elaborates on the structure, function, and signaling pathways of TLR4 and NF-κB p65 proteins in the pathogenesis of otitis media, aiming to provide more precise targets and better therapeutic efficacy for the diagnosis and treatment of otitis media. The role of inflammation in disease.
文摘Objective: To explore the underlying molecular mechanisms of cellular response to the challenge by 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of PC12 cells, an in vitro cell model for Parkinson’s disease, and the effect of NF-κB activation on the protection of Parkinson’s disease by Isoflavone (I). Methods: PC12 cells were used to establish the cell model of Parkinson’s disease, and are divided into five groups: control group;MPP+ group;I (Isoflavone) + MPP+ group;I group;SN-50 + MPP+ group. The content of NF-κB in PC12 cells was determined by immunocytochemistry;The viability of PC12 cells after treated with cell-permeable NF-κB inhibitor SN-50 and cell viability were measured by MTT assay;the expression levels of NF-κB p65 in cytoplasm and nuclear fractions were evaluated by western blot analysis;the mRNA expression of NF-κB p65 was analyzed by in situ hybridization (ISH). Results: Compared with the control group, the protein of NF-κB p65 both in cytoplasm and in nuclei was significantly higher than in I + MPP+ and MPP+ groups;similarly, the mRNA expression level of NF-κB p65 gene was also significantly higher;moreover, the protein expression of NF-κB p65 was much lower in I group (P + group, the protein of NF-κB p65 was significantly lower in I + MPP+ group, the mRNA expression level of NF-κB p65 gene was also significantly lower, and the protein expression level of NF-κB p65 was much lower in I + MPP+ group (P + group (P > 0.05). Conclusion: NF-κB activation is essential to MPP+-induced apoptosis in PC12 cells;but Isoflavone can inhibit the cell damage to some extent to execute its protective function, which may be involved in nigral neurodegeneration in patients with Parkinson’s disease.
文摘Nuclear factor kappa B(NF-κB) is one of the best-characterized transcription factors playing important roles in many cellular responses to a large variety of stimuli,including inflammatory cytokines, phorbol esters, growth factors, and bacterial and viral products. The aim of this study is to demonstrate NF-κB expression in the mouse cochlea and its enhancement in response to lipopolysaccharides(LPS) and kanamycin(KA) treatment. Methods KA treatment consisted of subcutaneous KA injections at 700 mg/kg twice a day with an eight-hour interval between the two injections for 3 or 7 days. For animals in the LPS treatment group, a single dose of 0.3 mg LPS dissolved in 0.2 ml sterile saline were injected into both bullae through the tympanic membrane and kept there for 3 hours. Animals in the control group received subcutaneous saline injection for 7 days. Following immmunohistochemichal processing with rabbit polyclonal anti-NF-κB p65 antibodies, cryosections of the cochlea were examined for expression of NF-κB p65 in various structures in the cochlea. Results NF-κB p65 expression, identified by presence of brown reaction products characteristic of DAB immunohistochemistry, was visible in the spiral ligament, spiral prominence, tectorial membrane(TM), spiral ganglion and nerve fibers. Relatively weak NF-κB p65 expression was also visualized in the organ of Corti. Within the organ of Corti, the inner hair cells(IHC), outer hair cells(OHC), inner pillar cells(IP), outer pillar cells (OP), Deiter’s cells(DC), and Boettcher’s cells exhibited stronger staining than the inner sulcus cells, Hensen’s cells(HC) and Claudius’cells. No NF-κB p65 expression was seen in the nucleus of the IHC and OHC. NF-κB p65 expression was increased in animals exposed to LPS or KA, demonstrating significant differences in the staining between control animals and LPS/KA-treated animals. NF-κB p65 expression was not significantly different between LPS treated and KA treated animals or between 3 and 7 days in KA-treated animals. Conclusion LPS and KA exposure increases expression of NF-κB p65 in the mouse cochlea.
基金supported by the Leibniz Association,Germany,and the VELUX Foundation,Switzerland
文摘Activation of nuclear factor kappa B （NF-κB） is a hallmark of various central nervous system （CNS） pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-~B in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans- dominant negative mutant of its upstream regulator IκBa, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro- gram in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.
基金Supported by grants from National Natural Science Foundation of China, No. 30471614 (to DK Qiu) and No.30571730 (to X Ma)Shanghai Leading Academic Discipline Project, No.Y0205 (to X Ma)
文摘To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B （NF-KB） were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines （interferon-y, IL-12, IL-1β and TNF-α） were observed.RESULTS： The activity of p38 MAPK and NF-~：B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~：B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.
文摘背景:基于核转录因子κB通路探究神经炎症的靶向治疗越来越值得探究,中药靶点多、范围广、机制丰富及不良反应少等优点在治疗各类疾病时都具有十分巨大的潜力。目的:基于核转录因子κB信号通路,对近年研究中出现的山奈酚、红花黄、汉黄芩苷及雷公藤甲素等中药单体治疗脊髓损伤后神经炎症的研究进展进行系统的阐述与归纳。方法:以“脊髓损伤,炎症,抗炎,中药单体,单体化合物,NF-κB信号通路,黄酮,糖苷,酚类,酯类,生物碱”为检索词在中国知网数据库中进行检索;以“Spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids”为检索词在PubMed数据库中进行检索,最终共纳入67篇文献进行综述分析。结果与结论:①核转录因子κB信号通路在神经系统中的作用复杂多样,能够调控中性粒细胞、小胶质细胞、星形胶质细胞和巨噬细胞等,介导损伤后炎症的发生与发展;②中药单体如汉黄芩苷对核转录因子κB抑制蛋白的降解、红花黄素对核转录因子κB信号通路磷酸化过程的抑制、山奈酚对核转录因子κB信号通路p65核易位的抑制等作用可以降低炎症反应对机体造成的影响,从而促进神经功能恢复;③核转录因子κB信号通路在损伤早期能够促进炎症反应和免疫细胞迁移活化,在损伤中后期能够促进损伤部位的修复和纤维化的发生等,适当的激活核转录因子κB信号通路具有促进炎症因子的释放、提高细胞的抗氧化能力及促进免疫细胞的活化等能力,但过度激活的核转录因子κB信号通路则容易导致慢性炎症的发生和持续、细胞凋亡受到抑制等;④未来的研究可以进一步探索如何准确调控核转录因子κB信号通路的活化水平、如何实现对神经系统炎症和损伤的精准干预展开,也可围绕中药单体的制备及中药单体对信号通路的作用机制展开,以期为神经系统疾病的康复和功能恢复提供更有效的治疗策略。
基金Shenzhen Science and Technology Plan(No.JCYJ20180306172419505).
文摘Objective: To investigate the expression relationship between nuclear transcription factor kappa B1 (NFκB1) and long non-coding RNA PACER (LncRNA-PACER) in peripheral blood mononuclear cells (PBMCs) of patients with pulmonary tuberculosis. Methods: From February 2018 to March 2019, 40 patients with pulmonary tuberculosis (tuberculosis group) and 40 healthy persons (control group) were collected, the levels of TNF-α, IL-6 and IL-8 in serum were detected by enzyme-linked immunosorbent assay (ELISA);the expressions of LncRNA-PACER and NFκB1 mRNAs in PBMCs were detected by real-time fluorescence quantitative PCR;Western blot was used to detect the expressions of NFκB1 and COX 2 in PBMCs;Pearson method was used to analyze the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis, and the expressions of LncRNA-PACER and NFκB1 in PBMCs of patients with pulmonary tuberculosis were analyzed. Results: Compared with the control group, the expressions of TNF-α, IL-6 and IL-8 in the serum of patients with pulmonary tuberculosis was significantly increased (P<0.05), and the expressions of LncRNA-PACER, NFκB1 mRNAs, proteins and COX-2 protein in PBMCs were significantly increased (P<0.05). The expressions of LncRNA-PACER and NFκB1 proteins in PBMCs were related to the number of pulmonary lesions and pulmonary cavity (P<0.05), and there was a positive correlation between the expression of LncRNA-PACER and the expression of NFκB1 mRNA in PBMCs of patients with pulmonary tuberculosis (r = 0.873, P<0.05). Conclusions: The expressions of NFκB1 and LncRNA-PACER in PBMCs of patients with pulmonary tuberculosis are significantly increased, they are positively correlated and both of them are related to the occurrence and development of pulmonary tuberculosis.
