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Nuclear factor (NF)-κB,a kind of protein transcription factor,mediates inflammation and other complex biological processes,and is a key regulator of many immune and inflammatory pathways,cell proliferation,differentiation and apoptosis.Psoriasis is an inflammatory skin disease characterized by increased levels of phosphorylated NF-κB,which leads to an increase in anti-apoptotic activity of keratinocytes and aggravation of inflammatory reactions.This review summarizes advances in NF-κB signaling pathway and its role in psoriasis.
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Ependymoma is the third most common pediatric primary brain tumor. Ependymomas are categorized according to their locations and genetic abnormalities, and these two parameters are important prognostic factors for patient outcome. For supratentorial (ST) ependymomas, RELA fusion-positive ependymomas show a more aggressive behavior than YAP1 fusion-positive ependymomas. Extracranial metastases of intra-axial neuroepithelial tumors are extremely rare. In this paper, we report a case of aggressive anaplastic ependymoma arising in the right frontoparietal lobe, which had genetically 1q25 gain, CDKN2A homozygous deletion, and L1CAM overexpression. The patient was a 10-year-old boy who underwent four times of tumor removal and seven times of gamma knife surgery. Metastatic loci were scalp and temporalis muscle overlying primary operation site, lung, liver, buttock, bone, and mediastinal lymph nodes. He had the malignancy for 10 years and died. This tumor is a representative case of RELA fusion-positive ST ependymoma, showing aggressive behavior.
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Child , Humans , Male , Brain Neoplasms , Buttocks , Ependymoma , Genetics , Liver , Lung , Lymph Nodes , Neoplasm Metastasis , Neoplasms, Neuroepithelial , Neural Cell Adhesion Molecule L1 , Scalp , Supratentorial Neoplasms , Transcription Factor RelAABSTRACT
Objective To observe the effect of the nuclear factor (NF)-κB inhibitor on the inflammatory injury and the secondary remote damage in remote areas of the CA1 region in the right hippocampus of the focal cerebral ischemic/reperfusion rats,and the NF-κB essential modifier binding domain (NBD) peptide was used to inhibit the activation of NF-κB signaling pathway to explore the function and mechanism of the NBD peptide in restraining inflammatory injury and reducing secondary remote damage in the hippocampus CA1 region.Methods According to the random number table,the male Sprague-Dawley (SD) rats were randomly divided into a sham group (n =24),an ischemia/reperfusion (I/R)group (n =38),a NBD group (n =38) and a modified type peptide (MT-NBD) group (n =38),then at the time point of 24 h and 7 d after reperfusion,the above 4 groups were divided into 2 subgroups.The experimental models were made by middle cerebral artery occlusion (modified line plug method) for 2 hours.The NBD peptide and the MT-NBD peptide were respectively injected into the right hippocampus of the experimental groups.The injury of neurons was examined by the methods of H&E and Fluoro-Jade B-(FJB)staining.The levels of interleukin-1β (IL-1β) and IL-1Ra were detected by using enzyme-linked immunosorbent assay.The protein expressions of NF-κB p65 and IκBα were analyzed by Western blotting and the double-labelling immunofluorescence.Results Compared with the NBD group (24 h 0.206 ±0.013,7 d 0.090 ±0.012) and the sham group (24 h 0.120 ±0.007,7 d 0.100 ±0.014),the NF-κB p65 protein expression in the I/R group (24 h 2.340 ± 0.101,7 d 2.440 ± 0.081) was increased significantly (q =64.431,66.704,67.747,56.624,all P ＜ 0.05).The level of IL-1β was remarkably increased in the I/R group (24 h (1.850 ±0.192) ng/ml,7 d (1.000 ±0.178) ng/ml) compared with the NBD group (24 h (1.250 ± 0.211) ng/ml,7 d (0.560 ± 0.183) ng/ml,q =10.730,9.710,P ＜0.05).The percent of survival neurons was significantly lower in the I/R group (24 h 27.50％ ± 3.59％,7 d 28.10％ ±4.46％) and the MT-NBD group (24 h 27.30％ ±4.53％,7 d 26.30％ ±5.03％)than the NBD group (24 h 58.90％ ± 3.46％,7 d 68.40％ ±4.20％,q =19.949,19.731,2.139,22.249,all P ＜0.05).The FJB staining showed that the number of neuron degeneration in the I/R group (24 h 28.10 ±2.13,7 d 29.50 ±2.45) was higher than the NBD group (24 h 12.50 ±2.41,7 d 9.30 ±2.52,q =3.211,4.521,P ＜ 0.05).Compared with the other three groups (sham group:24 h 0.130 ± 0.008,7 d 0.150 ±0.010;I/R group:24 h 1.340 ±0.213,7 d 1.750 ±0.119;MT-NBD group:24 h 1.250 ±0.114,7 d 1.620 ±0.097),the IκBα protein expression in the NBD group (24 h 1.680 ±0.148,7 d 2.010 ±0.085) was significantly increased (q =6.348,9.139,9.414,1.711,5.277,5.555,all P ＜0.05).Compared with the I/R group (24 h (0.570 ± 0.028) ng/ml,7 d (0.430 ± 0.039) ng/ml) and the MT-NBD group (24 h (0.490 ± 0.042) ng/ml,7 d (0.380 ± 0.018) ng/ml),the level of IL-1Ra in the NBD group (24 h (1.390 ± 0.055) ng/ml,7 d (1.250 ± 0.043) ng/ml) was remarkably increased (q =4.577,6.205,9.683,6.389,all P ＜ 0.05).The results between the I/R group and the MT-NBD group were not significantly different.Conclusions The research shows that NBD peptide treatment contributes to altering the NF-κB p65/IκBα expression in nucleus effectively.And it directly regulates the NF-κB activation to alleviate the inflammatory injury in the hippocampus CA1 region after the secondary remote damage.
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Objective To observe the roles of nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1 o (HIF-1 α) in hippocampal neurodegeneration of status epilepticus (SE) rats, and explore whether HIF-1α activation is regulated by NF-κB.Methods A total of 110 male Sprague-Dawley rats were randomly divided into seven groups : (1) Control group treated with saline (control, n =15), (2) sham group implanted cannula into lateral ventricle and treated with saline (sham, n =15), (3) SE group treated with pilocarpine (SE, n =20), (4) NF-κB activity inhibitor pyrrolidine dithiocarbamate (PDTC) group treated only with PDTC (PDTC, n =15), (5) SE + PDTC group treated with pilocarpine plus PDTC (SE + PDTC, n =15), (6) SE + HIF-1o siRNA group implanted cannula into lateral ventricle and treated with pilocarpine plus HIF-1 α siRNA (SE + HIF-1α siRNA, n =15), (7) SE + control siRNA group implanted cannula into lateral ventricle and treated pilocarpine plus control siRNA (n =15).SE was induced by injecting lithium chloride and pilocarpine.The seizure of rats was observed.The protein expressions of NF-κB and HIF-1 α in hippocampus of rats were examined by Western blotting.The degenerating neurons in hippocampus were detected by Fluoro-Jade C (FJC) staining.Results Twenty-four hours after termination of SE, the nuclear protein expressions of NF-κB and HIF-1α in hippocampus of rats were increased in SE group (0.57 × 0.06, 0.47 ± 0.07) compared with those in control group (0.23 ± 0.03, 0.20 ± 0.03;P ＜0.05);and compared with SE group PDTC significantly decreased the nuclear protein expressions of NF-κB and HIF-1 α in SE + PDTC group (0.23 ± 0.03, 0.14 ± 0.03;P ＜ 0.05);in SE + PDTC group the numbers of FJC positive cells in CA1 area (28.33 ±5.03) were decreased compared with that in SE group (76.67 ± 13.32);HIF-1 o siRNA injected into lateral ventricle of rats significantly decreased the expression of HIF-1α in hippocampus (0.22 ±0.03) and the number of FJC positive cell in CA1 area (27.34 ±7.02) in SE + HIF-1α siRNA group compared with those in SE group (0.39 ±0.06, 76.67 ± 13.32;P ＜0.05).Conclusions These data suggest that SE can result in activation of NF-κB/HIF-1o pathway in brain.Inhibition of the pathway can attenuate hippocampal neurodegeneration caused by SE, which has the brain protective effect.
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ObjectiveTo investigate the relationship of lymphotoxin β receptor (LTβR) and classical nuclear factor-κB (NF-κB) activation pathway in the pathogenesis and progress of cystitis and bladder cancer.MethodsThe LTβR and P65 mRNA expression were detected by Real-time quantitative PCR in 108 cases of fresh bladder tissue specimens (75 cases of bladder cancer,10 cases of inflammation and 23 normal bladder mucosa cases grouped by the tissue classification ),and protein expression were analyzed by immunohistochemistry assay in 118 cases of paraffin-embedded biopsy specimens (73 cases of bladder cancer,30 cases of cysitis and 15 normal bladder mucosa cases).The correlation analysis between the expressions of LTβR and P65 with clinical pathological data was then performed.Differences between LTβR and P65 mRNA and protein expression level were compared in different groups of bladder tissues using Kruskal-Wallis H test and the Chi-square test.Results( 1 )The mRNA expressions of LTβR and NF-κB/P65were higher in bladder cancer than those in normal group ( LTβR:29.4 ( 14.2 - 46.7 ) × 10 - 3/1.2 ( 0.3 -7.0) ×10-3,Z=-5.508; P65:9.7 (2.7 -21.1) ×10-3/1.0(0.8 ～1.8) ×10-3,Z=-5.030,P＜0.05 ).There were significantly differences between bladder cancer with different histological grades ( LTβR:18.2(2.1-31.3) × 10-3/ 28.4(16.6-36.2) × 10-3/47.9(34.3 -70.5) ×10-3,x2K-W=20.378;P65:4.9(1.3 - 12.0) × 10-3/7.4(3.0-21.9) × 10-3/17.0(10.0 ～28.3)× 10-3 ,x2K-W2 =15.219,P all ＜0.05) and lymph node metastasis (LTβR:27.2(9.7-40.1) ×10-3/39.4(26.7 -52.6) ×10-3,Z=-2.552; P65:7.4(2.3-15.6) ×10-3/13.4(6.7-23.3) ×10-3,Z=-2.026,P＜0.05).(2)The positive rates of LTβR and phosphorylated P65 ( p-P65 ) protein in cancer were higber than those of normal group (LTβR:69.8％/13.3％,x2 =16.600 ; p-P65:56.2％/6.7％,x2 =12.220,P ＜ 0.05 ).Upregulation of LTβR and p-P65 were associated with the histological grade (LTβR:56.3％/70.0％/90.4％,x2 =7.055; p-P65:40.6％ /60.0％/76.2％,x2 =6.679,P ＜0.05) and with lymph node metastasis (LTβR:58.3％/92.0％,x2 =8.849; p-P65:52.1％/64.0％,x2 =5.088,P ＜0.05).(3)There was a positive correlation between LTβR and P65 expression ( mRNA:r =0.654,P ＜ 0.05,protein:r =0.399,P ＜ 0.05 )in the bladder cancer and cystitis (r =0.521,P＜0.05).ConclusionsThe activation of LTβR and P65 was associated with progression and metastasis of bladder cancer.The activation of classical NF-κB pathway by LTβR may be achieved by P65.
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Objective To investigate the expression of TLR4 mRNA and NF-κB p65 in colorectal carcinomas and adjacent normal colon tissue, and evaluate their roles in the pathogenesis and development in colorectal carcinoma. Methods Sixty-three colorectal carcinoma samples and respective adjacent normal colon tissue samples ( well differentiated : 23 cases; moderately differentiated: 17 cases; poorly differentiated:20 cases; other differentiated type: 3 cases; lymph node metastasis: 27 cases; no lymph node metastasis:36 cases; Dukes A: 18cases;Dukes B: 14 cases Dukes C: 22 cases; Dukes D: 9 cases) were collected. The expression of TLR4 mRNA in colorectal carcinomas and adjacent tissue were detected by RT-PCR. The expression of NF-κB p65 was detected by WB. Results The expression of TLR4 mRNA in colorectal carcinomas and adjacent tissue were 86.42 ± 15.16 and 32.74 ± 9.44. It was significantly higher in carcinoma tissue than that in adjacent tissue ( t = 22.354, P ＜ 0.01 ). The expression of TLR4 mRNA in well, moderately and poorly differentiated coiorectal carcinomas were 69.58 ± 11.27, 64.57 ± 13.91 and 97.12 ± 15.44 respectively. TLR4 mRNA in poorly differentiated colorectal carcinomas was significantly higher than that in well, moderately differentiated ones ( t = 11.304 and 12.223, P ＜ 0.01 ). There was no difference between lymph node metastatic carcinomas ( 89.91 ± 13.33 ) and carcinomas without metastasis (81.16±13.59,t =0.959,P＞0.05). The expression of TLR4 mRNA in the Dukes A stage tumors (59.05±11.66) was lower than that in Dukes B(90.34 ±0.08),C(91.41 ± 15.21), D(101.46 ±17.43), respectively ( t = 8.708,9.664,9.525, P ＜ 0.05 ). The expression of NF-κB p65 in colorectal carcinoma(0.63 ±0.11) was significant higher than that in adjacent tissue(0.34 ±0.08,t = 18.266,P ＜0.01 ). The expression of NF-κB p65 in well, moderately and poorly differentiated colorectal carcinomas were 0.46 ± 0.09, 0.72 ± 0.11 and 0.77 ± 0.14, respectively. The experssion of NF-κB p65 in well differentiated colorectal carcinomas was obviously lower than the woderately and poorly differentiated carcinomas (t = 11.223 and 10.875, P ＜0.01 ). There was significant difference between the expression of p65 in lymph node metastatic carcinomas(0.82 ± 0.17) and non-metastatic carcinomas(0.57 ± 0.12, t =18.269,P＜0.05). The expression of NF-κB p65 in Dukes A colorectal carcinomas (0.39 ± 0.06) was lower compared with the Dukes B(0.72 ±0.12), C(0.69 ±0.14) and D carcinomas(0.76 ±0.13,t =10.442, 9.889 and 9.721, P ＜ 0.01 ). Conclusions The enhanced expression of TLR4/NF-κB p65 are closely associate with clinical stage and pathologic grade. NF-κB p65 may be an molecular marker of lymph node metastatic. The increased expression of TLR4/NF-κB p65 promote the pathogenesis and development of colorectal carcinoma.
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Objective To study the quantitative expression and the correlation of the NF-κB p65,COX-2 and MMP-9 Drotein in the hypopharyngeal carcinoma tissue.Methods FCM method was performed to detect the quantitative expression of the NF-κB p65,COX-2 and MMP-9 protein in 48 cases of hypopharyngeal carcinoma fresh sample and 48 cases of para-carcinoma tissue.Fluorescence Index wasdeftned as the quantitative expression index of the three proteins.Results The quantitative expression of the NF-κB p65,COX-2 and MMP-9 in hypopharyngeal carcinoma tissues(1.16,1.32 and 1.26) was remarkably higher than in para-carcinoma(1.03,1.04 and 1.04).The quantitative expression of three proteins in metastasis group was obviously higher than in non-metastasis group.The expression of NF-κB p65 and COX-2 protein in hypopharvngeal carcinoma tissues was positively related (P＜0.05). Conclusion The high expression of NF-κB p65 and COX-2 is closely related in hypopharyngeal carcinoma tissues.NF-κB p65 might improve the expression of COX-2.
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Objective To investigate the possible mechanism of curcumin inhibition to murine melanoma growth.Methods Melanoma cell line B16F10 was injected subcutaneously into the outer side of mouse right thigh to establish a melanoma-bearing mouse model.Seven days after the establishing the model, these mice were treated with intraperitoneal injection of curcumin at 50 and 100 mg/kg respectively or RPMI 1640 culture medium as control.Fourteen days later,the mice were killed,tumor weight was calculated;the tumor nuclear factor?B activity and survivin mRNA expression were measured by Western blot and RT-PCR,respectively.Results The tumor weight was significantly lower in the curcumin-treated mice than that in the controls (P