Interferon regulatory factor 2 binding protein 2:a new player of the innate immune response for stroke recovery

Ischemic brain injury triggers an inflammatory response. tissue but can also exacerbate brain injury. Microglia are This response is necessary to clear damaged brain the innate immune cells of the brain that execute this critical function. In healthy brain, microglia perform a housekeeping function, pruning unused syn- apses between neurons. However, microglia become activated to an inflammatory phenotype upon brain injury. Interferon regulatory factors modulate microglial activation and their production of inflammatory cytokines. This review briefly discusses recent findings pertaining to these regulatory mechanisms in the context of stroke recovery.

DNA-dependent activator of interferon-regulatory factors inhibits hepatitis B virus replication

AIM: To investigate whether DNA-dependent activator of interferon-regulatory factors (DAI) inhibits hepatitis B virus (HBV) replication and what the mechanism is. METHODS: After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plasmid, viral protein (HBV surface antigen and HBV e antigen) secretion was detected by enzyme-linked immunosorbent assay, and HBV RNA was analyzed by real-time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 (IRF3) phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-B (NF- B) activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Transwell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS: Viral protein secretion was significantly reduced by 57% (P < 0.05), and the level of total HBV RNA was reduced by 67% (P < 0.05). The viral core particle-associated DNA was also dramatically down-regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-B signaling was essential for DAI to elicit antiviral response in Huh7 cells. When the NF-B signaling pathway was blocked by a NF-B signaling suppressor (I B -SR), the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was independent of IRF3 signaling and secreted cytokines. CONCLUSION: This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is associated with activation of NF-B but independent of IRF3 and secreted cytokines.

Association of rs10954213 Polymorphisms and Haplotype Diversity in Interferon Regulatory Factor 5 with Systemic Lupus Erythematosus: A Meta-analysis

The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 （1RF5） play a special role in systemic lupus erythematosus （SLE） but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios （ORs） and the corresponding 95% confidence interval （95% CI）. A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results in- dicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rS10954213 G allele （A vs. G, P〈0.00001） in all subjects. The same pattern of the results was also ob- tained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele （49.1%） than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele （62.1%）. The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 （P=0.002）. The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 （P=-0.004）. This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype （rs2004640-rs2070197-rs10954213） in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.

Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-β1,vascular endothelial growth factor,and basic fibroblast growth factor in patients with chronic hepatitis C

AIM:To assess the role of transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)andbasic fibroblast growth factor(bFGF)in the pathogenesisof fibrosis associated with chronic hepatitis C(CHC)and to evaluate the influence of the antiviral therapyon above parameter levels depending on the treatmentresults(complete response or no response).METHODS:Study group included 100 patients withCHC,in whom fibrosis in liver specimens was assessed(Scheuer fibrosis score:1-4 points).Control groupincluded 30 subjects with antibodies anti-HCV presentand persistently normal ALT level,without fibrosis(Scheuer fibrosis score:0 points).Concentration ofstudied parameters was assayed in the serum byimmunoenzymatic method before and after the therapywith interferon alpha-2b and ribavirin.RESULTS:TGF-β1 levels were significantly higher in thestudy group compared to the control group(35.89 vs 32.37ng/mL;P=0.023).Such differences were not found in VEGFand bFGF levels.In patients showing complete response(negative HCV RNA and normal ALT level),significantincrease in VEGF(112.8 vs 315.03 pg/mL;P<0.05)andbFGF(2.51 vs 15.79 pg/mL;P=0.04)levels were found.Significant decrease in TGF-β1 level was observed bothin responders(37.44 vs 30.02 ng/mL;P=0.05),andin non-responders(38.22 vs 30.43 ng/mL;P=0.043).bFGF levels before the treatment were significantly lower(2.51 vs 5.94 pg/mL;P=0.04),and after the treatmentsignificantly higher(15.79 vs 4.35 pg/mL;P=0.01) in patients with complete response than in those with noresponse.CONCLUSION:Among the analyzed parametersTGF-β1 seems to play the most important role in thepathogenesis of fibrosis in CHC.Levels of this factor aresignificantly lower in subjects who do not have fibrosisdeveloped in them.Good therapeutic effect in CHCpatients is associated with significant changes in TGF-β1,VEGF,and bFGF levels,bFGF seems to have the highestusefulness in the prognosis of treatment efficacy.

Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

AIM:To study predictive factors of thyroid dysfunction associated with interferon-alpha(IFNα) therapy in chronic hepatitis C(CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction.METHODS:We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004.RESULTS:Thyroid disorder developed in 30/301(10%) patients with a mean delay of 6 ± 3.75 mo:13 patients had hyperthyroidism,11 had hypothyroidism,and 6 had biphasic evolution.During a mean follow-up of 41.59 ± 15.39 mo,9 patients with hyperthyroidism,3 with hypothyroidism,and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo.Recovery rate of dysthyroidism was not modified by treatment discontinuation,but was better for patients with negative thyroid antibodies before antiviral treatment(P = 0.02).Women had signif icantly more dysthyroidism(P = 0.05).Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism(P < 0.0003 and P = 0.0003,respectively).In a multivariate model,low fibrosis was found to be a predictive factor of dysthyroidism(P = 0.039).CONCLUSION:In this monocentric population of CHC,dysthyroidism,especially hyperthyroidism,developed in 10% of patients.Low fibrosis was found to be a predictive factor of dysthyroidism.Thyroid disorder recovered in 16/30 patients(53%) and recovery was better in the non-autoimmune form.

Effects of interferon-alpha on expression of hepatic stellate cell and transforming growth factor-pi and a-smooth muscle actin in rats with hepatic fibrosis

AIM: To investigate the effect of interferon-α (IFN-α) onpreventing or reversing hepatic fibrosis in rat experimental model induced by CCl4.METHODS: One hundred and ten Sprague-Dawley rats were divided into five groups: group A (normal controls, n = 18), group B (fibrotic model controls, n = 22), group C (IFN-α prevention, n = 22) initially treated with intramuscular injection of IFN-α in saline daily at the doses of 1×105 U for 6 wk, group D (IFN-α treatment, n = 24) treated with intra-muscular injection of IFN-α in saline daily atthe doses of 1×105 U for 6 wk after the first 6 wk, group E (0.9% sodium chloride treatment control, n = 24) treated with intra-muscular injection of 0.01 mL/kg daily for 6 wk after the first 6 wk. At the end of the experiment, all rats of each group were killed. Samples of the liver obtained by biopsy were subjected to histological, immunohistochemicaland electron microscopic studies for the expressions of transforming growth factor-β1 (TGF- β1) and α-smoothmuscle actin (α-SMA).RESULTS: The expressions of TGF-β1, the number of activated hepatic stellate cells and α-SMA in hepatic tissue of group C were significantly less than those of group B (P＜0.01). The degree of fibrosis score in group B was also significantly less than that of group C under light microscope (P＜0.01).CONCLUSION: IFN-α can inhibit the production of TGF-β1,decrease HSC activation and stimulate its apoptosis.

Clinical Value of Vascular Endothelial Growth Factor Combined with Interferon-γ in Diagnosing Malignant Pleural Effusion and Tuberculous Pleural Effusion

In order to investigate the clinical value of vascular endothelial growth factor （VEGF） combined with interferon-γ （IFN-γ） in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen （CEA）, VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase （ADA） activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve （AUCR^ROC） of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve （ROC）, The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group （P〈0,01）, The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio （88,7%, 99,8%, 94,4%, 0.96 respectively） were higher than those of CEA （67.8%, 96.1%, 82,4%, 0.78 respectively） and VEGF （81,5%, 84,3%, 82.9%, 0.79 respectively）. The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ （85.7%, 96,4%, 90.9%, 0.94 respectively） were higher than those of ADA （80,2%, 87,6%, 83.8%, 0,81 respectively）. It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.

Effect of oxymatrine on interferon-gamma and tumor necrosis factor-alpha serum levels in an experimental rat model of autoimmune encephalomyelitis

BACKGROUND： Studies have demonstrated that experimental autoimmune encephalomyelitis （EAE） onset correlates with increased interferon-v （IFN-γ） and tumor necrosis factor-α （TNF-α） expression. Oxymatrine （OM） has been shown to inhibit autoimmune responses, but there are no reports showing that it could prevent the development of EAE. OBJECTIVE： To observe the effect of OM on serum levels of IFN-γ and TNF-α in a rat model of EAE.DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Experimental Animal Center of Henan Academy of Chinese Medicine and at the Key Disciplines Laboratory Clinical Medicine of Henan Province between July and December 2008. MATERIALS： OM was purchased from Chia-tai Tianqing Pharmaceutical, China; complete Freund＇s adjuvant was purchased from Sigma, USA. METHODS： Forty female Wistar rats were randomly assigned to four groups： EAE model （M）, low-dose OM treatment （OM-L）, high-dose OM treatment （OM-H）, and normal control （N, no immunization）, with 10 rats in each group. EAE was established in the M, OM-L, and OM-H groups following immunization with Guinea pig spinal cord homogenate and complete Freund＇s adjuvant. The M and N groups were intraperitoneally injected with normal saline （6.7 mL/kg per day）, the OM-L group received an intraperitoneal injection of OM （100 mg/kg per day）, and the OM-H group received OM （150 mg/kg per day）. MAIN OUTCOME MEASURES： At 16 days after immunization, the degree of histopathological changes in the spinal cord was assessed by hematoxylin-eosin stanining. Enzyme-linked immunosorbent assay was used to detect serum levels of IFN-γ, and radioimmunoassay was utilized to determine serum TNF-α level. Neurological scores were measured on a daily basis according to a 0-5 scale. RESULTS： Daily injections of OM, both high and low doses, resulted in decreased neurological scores in EAE rats （P〈0.01）, as well as reduced cellular infiltration in the spinal cord and decreased levels of serum IFN-γ and TNF-α （P〈 0.01）. CONCLUSION： OM reduced the onset and severity of EAE, which correlated with decreased IFN-γ and TNF-α expression.

Effect of interferon-γ and tumor necrosis factor-α on hepatitis B virus following lamivudine treatment

AIM:To evaluate anti-hepatitis B virus (HBV) activity and cytotoxicity of interferon (IFN-γ) and tumor necrosis factor (TNF-α) following lamivudine treatment of HepG2.2.15 cells.METHODS:HepG2.2.15 cells were treated with 2 mol/L lamivudine for 16 d (lamivudine group),cultured for 10 d,followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (cytokine group),or treated with 2 mol/L lamivudine for 10 d followed by 5 ng/mL TNF-α and 1000 U/mL IFN-γ for 6 d (sequential group),or cultured without additions for 16 d (control group).Intracellular DNA was extracted from 3 × 105 HepG2.2.15 cells from each group.The extracted DNA was further purified with mung bean nuclease to remove HBV relaxed circular DNA that may have remained.Both HBV covalently closed circular DNA (cccDNA) and HBV DNA were examined with real-time polymerase chain reaction.The titers of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were quantified with enzyme-linked immunosorbent assay.Cell viability was measured with the cell counting kit-8 assay.RESULTS:Compared to lamivudine alone (22.63% ± 0.12%),both sequential (51.50% ± 0.17%,P = 0.034) and cytokine treatment (49.66% ± 0.06%,P = 0.041) showed a stronger inhibition of HBV cccDNA;the difference between the sequential and cytokine groups was not statistically significant (51.50% ± 0.17% vs 49.66% ± 0.06%,P = 0.88).The sequential group showed less inhibition of HBV DNA replication than the lamivudine group (67.47% ± 0.02% vs 82.48% ± 0.05%,P = 0.014);the difference between the sequential and cytokine groups was not statistically significant (67.47% ± 0.02% vs 57.45% ± 0.07%,P = 0.071).The levels of HBsAg and HBeAg were significantly decreased in the sequential treatment group compared to the other groups [HBsAg:3.48 ± 0.04 (control),3.09 ± 0.08 (lamivudine),2.55 ± 0.13 (cytokine),2.32 ± 0.08 (sequential),P = 0.042 for each between-group comparison;HBeAg:3.48 ± 0.01 (control),3.08 ± 0.08 (lamivudine),2.57 ± 0.15 (cytokine),2.34 ± 0.12 (sequential),P = 0.048 for each between-group comparison].Cell viability in the cytokine group was reduced to 58.03% ± 8.03% compared with control cells (58.03% ± 8.03% vs 100%,P = 0.000).Lamivudine pretreatment significantly reduced IFN-γ + TNF-α-mediated toxicity of HepG2.2.15 cells [85.82% ± 5.43% (sequential) vs 58.03% ± 8.03% (cytokine),P = 0.002].CONCLUSION:Sequential treatment overcame the lower ability of lamivudine alone to inhibit cccDNA and precluded the aggressive cytotoxicity involving IFN-γ and TNF-α by decreasing the viral load.

Anti Cervix Cancer Activity of Co-immobilized Tumor Necrosis Factor-α and Interferon-γ

Tumor necrosis factor α （TNF-α） and interferon-γ （IFN-γ） are cytokines with strong antitumor activities. They were reacted with a photoactive arylazide-4-azidobenzoic acid, resulting in photoactive TNF-α and IFN-γ. The infrared （IR） spectra of these products showed the characteristic absorption of an azido group at 2127 cm^-1. By photo-immobilization, this modified TNF-α and IFN-γ were immobilized on polystyrene membranes for cell culture to prepare biomaterials. The micro-morphology of photoactive cytokines was observed with a scanning electron microscope （SEM）. The inhibitory effect on growth of Hela cells and inducing apoptosis activity of these two cytokines were analyzed by growth curve, transmission electron microscope （TEM） and fluorescence active cell sorter （FACS）. The results showed that co-immobilization of IFN-γ and TNF-α had significant inhibitory effect on growth of Hela cells, inhibitory rate up to 82%, and IFN-γ had obviously synergistic action.

Interferon Regulatory Factor 5 and Renin-Angiotensin-Aldosterone System Polymorphisms in Coronary Artery Disease: An Overview of Experimental and Clinical Studies

Heart diseases are the main cause of mortality in Mexico, being coronary heart disease the most frequent in the country. Its high prevalence makes important the study of the pathophysiology and the search for prognostic factors. Different genes and polymorphisms promote atherogenesis and coronary artery disease, they affect inflammatory and vascular pathological processes. Interferon regulatory factor 5 (IRF5) is associated with coronary heart disease, it promotes chronic inflammation and cytokines release;it could trigger immune reactions and its activating receptors express in the vascular endothelium. Besides, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are implied with coronary disease, they are found in angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and angiotensin-converting enzyme (ACE) genes. These genetic polymorphisms are associated with a prothrombotic state, endothelial dysfunction, and immune activation. Multiple experimental studies showed that chronic activation of RAAS and chronic expression of IRF5 generates an environment prone to the development of atherosclerosis, and autoimmune and cardiovascular diseases. Studying these specific genes and their relationship with coronary heart disease will allow a better understanding of the pathological process and possibly the quest for new treatments.

Chimeric oncogenic interferon regulatory factor-2 (IRF-2): Degradation products are biologically active

Interferon Regulatory Factor-2 (IRF-2) belongs to IRF family, was identified as a mammalian transcription factor involved in Interferon beta (IFNβ) gene regulation. Besides that IRF-2 is involved in immunomodulation, hematopoietic differentiation, cell cycle regulation and oncogenesis. We have done molecular sub-cloning and expression of recombinant murine IRF-2 as GST (Glutathione-S-Transferase)- IRF-2 fusion protein in E. coli/XL-1blue cells. Recombinant IRF-2 with GST moiety at N-terminus expressed as GST-IRF-2 (~66 kd) in E. coli along with different low molecular mass degradation products revealed approximately 30, 42, 60 and 62 kd by SDS-PAGE and Western blot, respectively. We further confirm that degradation takes place at C-terminus of the fusion protein not at N-terminus as anti-GST antibody was detecting all bands in the immunoblot. The recombinant IRF-2 was biologically active along with their degradation products in terms of their DNA binding activity as assessed by Electrophoretically Mobility Shift Assay (EMSA). We observed three different molecular mass DNA/protein complexes (1 - 3) with Virus Response Element (VRE) derived from human Interferon IFNβ gene and five different molecular mass complexes (1 - 5) with IRF-E motif (GAAAGT)4 in EMSA gel. GST only expressed from empty vector did not bind to these DNA elements. To confirm that the binding is specific, all complexes were competed out completely when challenged with 100-X fold molar excess of IRF-E oligo under cold competition. It means degradation products along with full-length protein are able to interact with VREβ as well as IRF-E motif. This means degradation products may regulate the target gene (s) activation/repression via interacting with VRE/IRF-E.

Inhibitory effect of interferon-α-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated in nude mice

AIM:To evaluate the effects of interferon-α-2b (IFN-α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α-2b against HCC growth. METHODS:Thirty-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells,the mice in test groups (groups A,B and C) received IFN-α-2b at a serial dose (10 000 IU for group A,20 000 IU for group B,40 000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS:Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P < 0.01),and the tumor growth inhibition rate in groups A,B and C was 27.78%,65.22% and 49.64%,respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P < 0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group (P < 0.01). Group B had a higher inhibition rate of tumor growth,a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P < 0.05),but there was no significant difference between groups A and C. CONCLUSION:The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.

Effect of interferon alpha2b plus ribavirin treatment on selected growth factors in respect to inflammation and fibrosis in chronic hepatitis C

AIM: Growth factors (GE) that participate in regeneration and apoptosis have an important role in chronic liver diseases. We analyzed serum GF concentration during antiviral treatment and correlated it with morphological liver failure in chronic hepatitis C.METHODS: The levels of GF were determined in sera by ELISA method in 0, 16, 32 and 48 wk of therapy in 40 patients treated with IFNα2b (9 MU sc/wk) and RBV (1.2 g/d) and in 25 healthy subjects. Blind liver biopsies were done before treatment with histological grading and staging examination.RESULTS: The hepatocyte growth factor (HGF) and epidermal growth factor (EGF) were markedly elevated prior the treatment and decreased during the therapy,although they did not reach the normal level. In nonresponding (NR) patients, HGF and EGF were higher than that in responders (R), however differences were not significant. Before the treatment thrombopoietin (TPO)level was significantly lower in R than in NR (P＜0.03).Platelet-derived growth factor (PDGF) concentration was lower in chronic hepatitis C than in healthy subjects and decreased during the treatment. A significant positive correlation was observed between inflammatory activity in the liver tissue and the concentration of HGF (in R: r= 0.4,in NR: r= 0.5), TPO (R: r= 0.6), and a significant negative correlation between this activity and EGF (R: r = -0.6)and PDGF (R: r = -0.5), Serum HGF concentration was higher in more advanced fibrosis (R: r = 0.5, P＜0.05;NR: r = 0.4, P＜0.03).CONCLUSION: The decrease in PDGF can be an effective prognostic marker of the treatment and HCV elimination.Decreasing HGF, EGF, and PDGF can influence the inhibition of inflammatory and fibrotic processes in the liver during the antiviral treatment.

巨噬细胞极化调控因子在脑卒中康复中的表达变化及其与认知功能恢复的关系

目的探讨巨噬细胞极化调控因子[干扰素调控因子8(IRF8)]在脑卒中康复中的表达变化及其与认知功能恢复的关系。方法这是一项横断面回顾性队列研究,数据来自2021年1月—2023年1月在保定市第二中心医院接受治疗的急性缺血性卒中患者,并在卒中后2周使用简易精神状态检查量表确定了卒中后认知障碍(PSCI)组(n=76)和非PSCI组(n=42)。RT-qPCR用于分析外周血单个核细胞(PBMCs)中IRF8基因表达。通过二元逻辑回归进行研究IRF8基因表达和认知结果之间的联系。结果PSCI组PBMCs中IRF8 mRNA表达显著高于非PSCI组(P<0.001)。在IRF8 mRNA三分位数中观察到PSCI和非PSCI患者比例的显著差异[T1:53.8%(21/39),T2:64.1%(25/39),T3:75.0%(30/40),χ2=8.082,P=0.018]。在Logistic回归分析中,IRF8 mRNA表达最高的三分位数(>0.024)(OR=1.956,P<0.001)、年龄(OR=1.062,P<0.001)、NIHSS评分(OR=1.145,P=0.014)、血红蛋白(OR=1.194,P=0.024)与PSCI风险较高显著相关。当截断值为0.01时,IRF8 mRNA预测PSCI的AUC为0.682,准确率为71.49%,特异度为50.24%,敏感度为71.42%。将IRF8 mRNA、年龄、NIHSS评分、血红蛋白纳入列线图中,其预测PSCI的AUC为0.862。结论缺血性卒中入院时PBMCs中IRF8 mRNA表达与卒中后急性期的PSCI相关。

MS19通过抑制IRF5表达调控巨噬细胞极化减轻CTD-ILD肺部炎症的作用研究

目的 探讨MS19通过靶向干扰素调节因子5(IRF5)对结缔组织疾病相关肺间质病变(CTD-ILD)小鼠模型肺部炎症的治疗作用及其相关机制。方法 动物实验:构建CTD-ILD小鼠模型,予以MS19干预,研究MS19对CTD-ILD小鼠肺部炎症的影响。细胞实验:对RAW264.7细胞进行OE-IRF5转染,然后予以MS19干预,研究MS19对IRF5调控的巨噬细胞M1型极化及炎症反应的影响。结果 动物实验:CTD-ILD小鼠出现明显的肺部炎症,小鼠支气管肺泡灌洗液(BALF)中IRF5的表达增高、巨噬细胞M1型极化增加及促炎因子(TNF-α、IL-6和IL-1β)的表达升高;而MS19干预后,CTD-ILD小鼠的肺部炎症减轻,BALF中IRF5表达降低、巨噬细胞M1型极化减少及促炎因子表达下降。细胞实验:脂多糖诱导巨噬细胞M1型极化、促炎因子表达增加;转染OE-IRF5后,巨噬细胞M1型极化增加、促炎因子表达增加;MS19干预后,巨噬细胞M1型极化减少、促炎因子表达减少。结论 MS19通过靶向抑制IRF5调控巨噬细胞极化及炎症反应,从而改善CTD-ILD的肺部炎症,为防治CTD-ILD提供潜在靶点和候选药物。

IRF8靶向铁死亡在急性肺损伤中的作用及机制研究

目的探讨干扰素调节因子8(interferon regulatory factor 8,IRF8)在急性肺损伤(acute lung injury,ALI)中的作用及其机制。方法采用实时荧光定量逆转录聚合酶链反应(RT-qPCR)和蛋白免疫印迹(WB)检测体内外ALI模型中IRF8 mRNA和蛋白的表达。体外构建稳定过表达和敲低IRF8的A549细胞系,采用RT-qPCR检测炎症相关基因mRNA的表达;WB检测凋亡相关基因的表达。分别选取12只同窝阴性对照小鼠和12只Irf8敲除品系小鼠,构建ALI模型,收集造模后的小鼠肺组织并称重;收集并检测肺泡灌洗液中总细胞数以及总蛋白含量。采用苏木精-伊红染色及免疫荧光分析肺组织炎症浸润情况;利用RT-qPCR检测Irf8敲除小鼠肺组织炎症相关基因mRNA的表达;TUNEL染色分析肺组织凋亡情况;采用WB分别在体内外ALI模型中检测铁死亡相关信号分子的蛋白表达。结果IRF8在体内体外ALI中表达上调;体外敲低IRF8加剧细胞内炎症以及细胞凋亡,反之,过表达IRF8可在体外ALI模型中发挥保护作用;敲除Irf8加重小鼠肺损伤;进一步机制探索发现IRF8通过调控铁死亡相关信号分子表达从而减轻肺损伤。结论IRF8通过靶向铁死亡在肺损伤中发挥保护作用,为肺损伤的治疗提供潜在靶点。

基于miR-155/TLR4/MyD88信号通路探讨蛇伤胶囊对竹叶青蛇伤的抗炎作用

目的探讨蛇伤胶囊对竹叶青蛇伤miR-155/Toll样受体4(TLR4)/髓样分化因子88(MyD88)信号通路及炎症的影响。方法将18只雄性新西兰大白兔分为对照组、模型组和蛇伤胶囊组,每组6只。对照组正常饮食饮水,另两组注射7.5 mg/kg竹叶青蛇毒液6 h后,模型组灌胃348 mg/(kg·d)生理盐水,蛇伤胶囊组灌胃348 mg/(kg·d)蛇伤胶囊,均连续灌胃1周。观察实验兔的一般行为学,qRT-PCR检测外周血中miR-155a-5p、TLR4和MyD88表达,ELISA检测血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、γ干扰素(IFN-γ)和白细胞介素-4(IL-4)含量。结果与对照组比较,模型组精神和食欲变差,排便稀软带血,伤口溃烂,miR-155-5p、TLR4 mRNA、MyD88 mRNA、IL-6和TNF-α表达均显著增加(均P<0.01),IFN-γ和IL-4表达显著下降(均P<0.01)。蛇伤胶囊组较模型组情况明显好转,miR-155a-5p、TLR4 mRNA、MyD88 mRNA、IL-6和TNF-α表达显著下降(均P<0.01),IFN-γ和IL-4表达显著增加(均P<0.01)。结论蛇伤胶囊抑制竹叶青蛇伤造成的炎症反应,维持Th1/Th2细胞平衡,其作用机制可能与抑制miR-155/TLR4/MyD88轴的表达有关。

激光联合干扰素治疗对阴道上皮内瘤变患者阴道微生态、炎症因子及预后的影响

目的分析激光联合干扰素对阴道上皮内瘤变(VAIN)患者的阴道微生态、炎症因子以及预后的影响。方法60例VAIN患者,按随机数字表法分为对照组和研究组,每组30例。对照组患者通过二氧化碳(CO_(2))激光治疗,研究组患者通过CO_(2)激光联合干扰素治疗。比较两组患者临床治疗效果;并发症发生情况;治疗前后炎症因子指标[肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、Toll样受体2(TLR2)];生存素(Survivin)、增殖细胞核抗原(Ki-67)阳性表达情况。结果研究组患者的临床治疗总有效率96.67%高于对照组的73.33%,差异有统计学意义(P<0.05)。治疗后,研究组患者的TNF-α(9.66±0.43)ng/L、IL-10(8.83±0.54)ng/L、TLR2(6.31±0.29)ng/L均低于对照组的(12.09±0.78)、(10.79±1.36)、(7.95±0.46)ng/L,差异有统计学意义(P<0.05)。治疗后,研究组患者Survivin阳性表达率(24.45±2.97)%、Ki-67阳性表达率(20.71±2.49)%低于对照组的(36.21±3.96)、(40.58±3.83)%,差异有统计学意义(P<0.05)。研究组并发症发生率为6.67%(2/30),与对照组的10.00%(3/30)比较,差异无统计学意义(P>0.05)。结论针对VAIN患者给予VAIN患者激光联合干扰素治疗的临床效果更佳,能够有效改善炎症因子指标及Survivin、Ki-67表达情况,减少患者并发症的发生,值得推广应用。

干扰素诱导蛋白10在呼吸道病原微生物感染诊断和疾病监测中的研究进展

干扰素诱导蛋白10(interferon inducible protein 10,IP-10)是Cys-X-Cys(CXC)趋化因子家族成员之一,其受体为CXCR3。IP-10具有多种生物学功能,如趋化T细胞、单核细胞、NK细胞在内的CXCR3+细胞到炎症部位发挥抗炎或促炎作用。研究发现,IP-10与呼吸道病原微生物感染及疾病进程相关,在结核感染的诊断,以及新型冠状病毒感染和高致病性禽流感等急性严重呼吸道感染性疾病进程的监测中发挥一定作用。因此,笔者主要围绕IP-10在各类呼吸道病原微生物感染的诊断及病程监测中的研究进展进行综述。