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interleukin-4 affects microglial autophagic flux

Neural Regeneration Research 2019年第9期14卷 1594-1602页

作者： Run-Hong Tang Rui-Qun Qi Hua-Yan Liu Department of Neurology the First Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Dermatology Key Laboratory of Immunodermatologythe First Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic ***,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/***,the role of interleukin-4 in microglial autophagy is *** view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 ***,light chain 3-II and p62 protein expression levels were detected by western blot ***2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 ***3-II and p62 protein expression levels were again detected by western blot *** addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent *** results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 ***-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic *** results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.

关键词： nerve regeneration Alzheimer’s disease interleukin-4 amyloid-β microglial autophagy microglial polarization microglia M1 phenotype M2 phenotype peptide degradation neural regeneration

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interleukin-4 promotes microglial polarization toward a neuroprotective phenotype after retinal ischemia/reperfusion injury

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Neural Regeneration Research 2022年第12期17卷 2755-2760页

作者： Di Chen Cheng Peng Xu-Ming Ding Yue Wu Chang-Juan Zeng Li Xu Wen-Yi Guo Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology ShanghaiChina

Glaucoma results from irreversible loss of retinal ganglion cells(RGCs)through an unclear *** polarization and neuroinflammation play an important role in retinal *** study aimed to explore the function of microglial polarization during glaucoma progression and identify a strategy to alleviate retinal *** ischemia/reperfusion injury was induced in C57BL/6 *** a separate cohort of animals,interleukin(IL)-4(50 ng/mL,2μL per injection)or vehicle was intravitreally injected after retinal ischemia/reperfusion *** loss was assessed by counting cells that were positive for the RGC marker RNA binding protein,mRNA processing factor in retinal flat *** expression of classically activated(M1)and alternatively activated(M2)microglial markers were assessed by quantitative reverse transcription-polymerase chain reaction,immunofluorescence,and western *** results showed that progressive RGC loss was accompanied by a continuous decrease in M2 microglia during the late phase of the 28-day period after retinal ischemia/reperfusion ***-4 was undetectable in the retina at all time points,and intravitreal IL-4 administration markedly improved M2 microglial marker expression and ameliorated RGC loss in the late phase post-retinal ischemia/reperfusion *** summary,we observed that IL-4 treatment maintained a high number of M2 microglia after RIR and promoted RGC survival.

关键词： glaucoma hyper-intraocular pressure in vivo interleukin-4 intravitreal injection M2 microglia neurodegeneration neuroprotective effect retinal ganglion cell retinal ischemia-reperfusion

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Effects of Intrinsic Nitric Oxide on the Expression of interleukin-4 and IFN-γ mRNA in the Bronchial and Lung Tissues of Sensitized Rats

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2000年第1期20卷 29-31页

作者：薛建敏徐永健张珍祥 Department of Respiratory Medicine Tongji Hospital Tongji Medical University Wuhan

Summary: To investigate the effects of intrinsic nitric oxide (NO) on the expression of interleukin-4 (IL-4) mRNA and interferon-γ (IFN-γ) mRNA in the airway inflammation of asthma, the rat models of asthmatic inflammation were established by sensitizing and then challenging the animals with ovalbumin. The 24 animals were randomly divided into control group, sensitized group, sensitized and L-Arg-treated group as well as L-NAME-treated group equally. By using in situ hybridization combined with compute physiological quantitative imaging analysis techniques, the influence of intrinsic NO on the expression of IL-4 mRNA and IFN-Y mRNA in the airway inflammatory cells was observed. In situ hybridization study demonstrated that IL-4 mRNA expres- sion was obviously increased as compared with that in the control group, mainly distributed in the inflammatory cells in the submucous of airways in the sensitized group. The increase of intensity of IL-4 mRNA expression was positively correlated with the numbers of eosinophil (Eos) and lymphocyte (both with P4 mRNA (P4 mRNA in inflammatory cells (P4 mRNA of Th2 lymphocytes and the expression of IFN-γ mRNA of Th1 lymphocytes and in turn, promote the development of asthmatic airway inflammation.

关键词： asthma nitric oxide interleukin-4 interferon-γ in situ hybridization

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The Akt/glycogen synthase kinase-3β pathway participates in the neuroprotective effect of interleukin-4 against cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2020年第9期15卷 1716-1723页

作者： Mei Li Wen-Wei Gao Lian Liu Yue Gao Ya-Feng Wang Bo Zhao Xiao-Xing Xiong Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Personnel Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

interleukin-4(IL-4) has a protective effect against cerebral ischemia/reperfusion injury. Animal experiments have shown that IL-4 improves the short-and long-term prognosis of neurological function. The Akt(also called protein kinase B, PKB)/glycogen synthase kinase-3β(Akt/GSK-3β) signaling pathway is involved in oxidative stress, the inflammatory response, apoptosis, and autophagy. However, it is not yet clear whether the Akt/GSK-3β pathway participates in the neuroprotective effect of IL-4 against cerebral ischemia/reperfusion injury. In the present study, we established a cerebral ischemia/reperfusion mouse model by middle cerebral artery occlusion for 60 minutes followed by a 24-hour reperfusion. An IL-4/anti-IL-4 complex(10 μg) was intraperitoneally administered 30 minutes before surgery. We found that administration of IL-4 significantly alleviated the neurological deficits, oxidative stress, cell apoptosis, and autophagy and reduced infarct volume of the mice with cerebral ischemia/reperfusion injury 24 hours after reperfusion. Simultaneously, IL-4 activated Akt/GSK-3β signaling pathway. However, an Akt inhibitor LY294002, which was injected at 15 nmol/kg via the tail vein, attenuated the protective effects of IL-4. These findings indicate that IL-4 has a protective effect on cerebral ischemia/reperfusion injury by mitigating oxidative stress, reducing apoptosis, and inhibiting excessive autophagy, and that this mechanism may be related to activation of the Akt/GSK-3β pathway. This animal study was approved by the Animal Ethics Committee of Renmin Hospital of Wuhan University, China(approval No. WDRY2017-K037) on March 9, 2017.

关键词： Akt/glycogen synthase kinase-3βpathway apoptosis autophagy cerebral ischemia/reperfusion injury infarct volume interleukin-4 neuroprotection oxidative stress

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Effects of aqueous extract from red Liriope platyphylla on phthalic-anhydride-induced atopic dermatitis in interleukin-4/Luciferase/Consensus non-coding sequence-1 transgenic mice evaluated in terms of luciferase signal and general phenotype biomarkers

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Journal of Traditional Chinese Medicine 2017年第4期37卷 475-485页

作者： Moon Hwa Kwak Ji Eun Kim Jun Go Hong Joo Son Hee Seob Lee Jin Tae Hong Dae Youn Hwang College of Natural Resources and Life Science/Life and Industry Convergence Research Institute Pusan National UniversityMiryang 627-706South of Korea College of Human Ecology Pusan National UniversityBusan 609-735south of Korea College of Pharmacy and Medical Research Center Chungbuk National UniversityChungju 361-763south of Korea College of Pharmacology Chungbuk National UniversityChungju 361-763south of Korea

OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phthalic anhydride(PA) treated interleukin-4(IL-4)/Luc/Consensus non-coding sequence-1(CNS-1) transgenic(Tg) mice following treatment with aqueous extract of RLP(AEt RLP) for4 ***: Alterations in AD phenotypes were measured in IL-4/Luc/CNS-1 Tg mice following treatment with AEt RLP using inflammation parameter analysis, bioluminescence imaging analysis, histological analysis, reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and Western blot ***: RLP contained high concentrations of total phenolic compounds, total flavonoid compounds and 5-HNE related to AD therapy. The Luc signal was only detected in the abdominal region and the submandibular lymph node(SL), mesenteric lymph node(ML), thymus and pancreas of the PA treated group. This signal was significantly decreased by 28%-73% throughout the body and in the four organs in PA + AEt RLP treated group. Furthermore, the lymph node weight, immunoglobulin E concentration and dermal thickness were decreased by 37%-67% in the PA + AEt RLP treated ***: Our findings suggest that the therapeutic effect of AEt RLP on PA induced AD could be successfully quantified by comparison of Luc signals and AD phenotype markers in IL-4/Luc/CNS-1Tg mice, and that the Luc signal was as sensitive as the general AD phenotypes, enabling detection of effects without euthanasia.

关键词： Dermatitis, Atopic Liriope plant interleukin-4 Luciferases Mice, transgenic Phthalic anhydrides Immunoglobulin E

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Effects of Micronutrients on Oxidative Stress and Islet Function in Type 1 Diabetes Mellitus Rats:Relationships to Th2 Type Cytokines,interleukin-4,and Interluekin-10

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Chemical Research in Chinese Universities 2007年第6期23卷 701-704页

作者： ZHANG Gui-zhen LI Mei-hua SONG Yang LIU Ting GAO Shen SUN Ying Department of Central Research The Third Clinical College Jilin University Changchun 130033 P. R. China Department of Allergy ＆ Clinical Immunology Faculty of Medicine Imperial College School National Heart ＆ Lung Institute Dovehouse Street London SW3 6LY UK

To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats＇ pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of IL-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients（p 〈0.01 and p 〈0.05, respectively） ; the blood glucose concentration decreased （p 〈 0. 05 ） ; both the functional β cell in islets and the insulin content in pancreatic tissue increased （p 〈 0. 05 and p 〈0. 01 ） ; the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively（p 〈0. 01 and p 〈 0. 05）. The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats .

关键词： Immanohistochemistry Oxidative stress Micronutrients T1 DM interleukin-4 Interluekin-10

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Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1473-1483页

作者： Chen Chen Chen-Yang Dai Fang Han Jia-Yin Wu Lin Sun Xin-Yi Wu Department of Ophthalmology Clinical Medical College of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Ophthalmology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Remodeling and Function Research Shandong UniversityJinan 250012Shandong ProvinceChina

AIM:To investigate the potential interactions of thymic stromal lymphopoietin(TSLP)with interleukin-4(IL-4)in adaptive immunity during fungal keratitis(FK).METHODS:An FK mouse model was induced with Aspergillus fumigatus(AF)hyphal *** were divided into several groups:untreated,phosphate buffer saline(PBS),infected with AF,and pretreated with a scrambled siRNA,a TSLP-specific siRNA(TSLP siRNA),murine recombinant TSLP(rTSLP),immunoglobulin G(IgG),murine recombinant IFN(rIFN-γ),murine recombinant IL-4(rI L-4),rIL-13,murine recombinant IL-17A(rIL-17A),and murine recombinant IL-17F(rIL-17F)*** realtime reverse transcription-polymerase chain reaction(qRTPCR)and enzyme-linked immunosorbent assay(ELISA)or Western blot were performed to determine mRNA and protein levels in the inflamed *** locations were observed by immunofluoresence staining after AF hyphal ***:Compared to those in the untreated group,TSLP and T helper type 1(Th1)cytokine levels in the AF group were upregulated at 24 h post infection(hpi),and those of T helper type 2(Th2)and T helper type 17(Th17)cytokines were increased at 5 d post infection(dpi).Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF *** TSLP level was increased in the rIL-4-pretreated group,but there were no significant changes among the other *** staining showed cytokine locations after AF hyphal ***:TSLP induces a Th2 immune response and promots Th2 T cell differentiation in ***-4 promotes TSLP ***,TSLP with IL-4 regulates adaptive immunity in FK.

关键词： Aspergillus fumigatus keratitis thymic stromal lymphopoietin Th2 immune response interleukin-4

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EFFECTS OF interleukin-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

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Chinese Medical Sciences Journal 1994年第2期9卷 125-128页

作者：朱康儿 KerryAtkinson DepartmentofHematology FirstAffiliatedHospitalZhejiangMedicalUniversityHangzhou310003 DepartmentofHematolosy St.Vincent′HospitalSydney2010Australia

We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo. IL-4 alone was found to be incapable of stimulating colony formation, but it inhibited both IL-3-and GM-CSF-induced colony formation by murine hematopoietic progenitor cells. In contrast, colony formation induced by G-CSF was enhanced in the presence of IL-4. We also studied the influence of IL-4 on hematopoietic reconstiution after allogeneic bone marrow transplantation in a murine medel, and found that IL-4 had significant inhibitory effects on neutrophil recovery and that neutrophil recovery accelerated by IL-3 and G-CSF was significantly suppressed by IL-4. The combination of IL-4 and GM-SF caused a significant decrease in the absolute number of neutrophils.

关键词： interleukin-4 hematopoietic progenitor bone marrow transplantation

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Effect of Ligustrazine Injection on Levels of interleukin-4 and Interferon-γin Patients with Bronchial Asthma

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Chinese Journal of Integrative Medicine 2008年第3期14卷 217-220页

作者：车晓文张颖王晖王伟 Department of Respiratory Medicine Second Hospital of Shandong University

Objective： To explore the effect of ligustrazine injection （LI） on serum levels of interleukin-4 （IL-4） and interferon- -γ （IFN- -γ ） in patients with bronchial asthma and determine the mechanism of action of LI in preventing and treating asthma. Methods： Sixty-eight patients with mild or moderate bronchial asthma were assigned to two groups equally according to their sequence number, odd or even. The conventional treatment was administered to both groups, and LI was given to the treatment group by ultrasonic spray inhalation twice a day but not to the control group. The therapeutic course for all was 2 weeks. Further, 30 healthy subjects who had no history of smoking were enrolled as the normal control group. The clinical condition scores, frequency of attacks and dosage of Terbutaline inhaled were scored and recorded on the first day of hospitalization （before treatment） and after treatment. At the same time, the indexes of lung function, including forced expiratory volume in one second （FEV1）, forced expiratory volume in one second to forced vital capacity ratio （FEV1%） and the peak expiratory flow （PEF） were determined before treatment. The levels of IL-4 and IFN--γ in peripheral blood were detected by ELISA before and after treatment, and compared with that of the healthy control group. Results： After treatment, the clinical condition scores were found to be lower, indexes of lung function were elevated, but serum level of IL-4 and ratio of IL-4/IFN-γwere reduced in both groups, showing significant differences as compared to those before treatment （P〈0.05）. However, the changes in all the indexes were more significant in the treatment group than in the control group, also showing statistical significance （P〈0.05）. No significant difference was revealed when IFN--γ levels were compared before and after treatment in both groups, though a lowering trend could be seen, significant difference could not be found in the comparison of IFN--γ levels between groups after

关键词： ligustrazine injection asthma lung function TH1/Th2 disequilibrium interleukin-4 interferon- -γ

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Recombinant adeno-associated virus-mediated inhibiting of interleukin-4 expression in rat model of asthma

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Chinese Medical Journal 2006年第3期119卷 223-225页

作者： CAO Yong XIONG Wei-ning XU Yong-jian ZHANG Zhen-xiang GAO Bao-an DU Chun-ling LU Jun-yu YE Tao Department of Respiratory Medicine Tongji Hospital TongjiMedical College Huazhong University of Science and TechnologyWuhan 430030 China

Asthma is a chronic disease characterized by ,reversible airway obstruction, airway hyperresponsiveness, and inflammation of airways, Th2 cells, one sort of CD4＋ T lymphocytes, are currently considered to play an important role in the chronic airway inflammation of asthma, Meanwhile, a number of laboratories have clearly established the importance of the Th2-dedved cytokine interleukin-4 （IL-4） in mediating the airway inflammatory response, Anti-IL-4 therapy might be beneficial in treatment of chronic asthma.

关键词： adeno-associated virus interleukin-4 asthma

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