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chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization

Cellular & Molecular Immunology 2014年第4期11卷 355-366页

作者： Yuli Lin Xuguang Yang Wenjie Yue Xiaofei Xu Bingji Li Linlin Zou Rui He Department of Immunology School of Basic Medical Sciences Shanghai China Department of Gastroenterology Huashan Hospital Shanghai China Biotherapy Research Center Fudan University Shanghai China

chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease （IBD）; however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin （aa 17-156） aggravated the severity of dextran sulfate sodium （DSS）-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-a and interferon （IFN-7）. Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 （Arg-1）, Yml, FIZZ1 and IL-IO, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis （UC） patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.

关键词： chemerin intestinal inflammation macrophage

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chemerin deficiency regulates adipogenesis is depot different through TIMP1

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Genes & Diseases 2021年第5期8卷 698-708页

作者： Cheng-Long Huang Liu-Ling Xiao Min Xu Jun Li Shu-Fen Li Cui-Song Zhu Yu-Li Lin Rui He Xi Li Biology Science Institutes Chongqing Medical UniversityChongqing400016PR China Center for Translational Research in Hematologic Malignancies Houston Methodist Cancer CenterHouston Methodist Research InstituteHoustonTX 77030USA Key Laboratory of Metabolic Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologyFudan University Shanghai Medical CollegeShanghai200032PR China Shanghai Public Health Clinical Center Fudan UniversityShanghai201508PR China Department of Immunology Fudan University Shanghai Medical CollegeShanghai200032PR China

Adipocytes and immune cells are vital for the development of adipose ***-pokines secreted by adipocytes regulate adipogenesis and body *** is one of the ***,the function and mechanism of chemerin in adipose tissue are not fully *** with wild type(WT)mice,Rarres2^(-/-)mice gained weight and significantly increased fat distribution in subcutaneous adipose tissue(SAT),rather than visceral adipose tissue(VAT)on high fat diet(HFD).PPARg and C/EBPa,the master regulators of adipogenesis,were up-regulated in SAT and down-regulated in VAT in Rarres2^(-/-)mice comparing with WT *** of chemerin deficiency or not,the ratio of adipocyte-progenitors to total cells and the differentiation capacity of adipocyte-progenitors were similar in SAT and VAT,but macrophage infiltration in VAT was more severe than in SAT in Rarres2^(-/-)***,CD45þimmune cells supernatant from Rarres2^(-/-)SAT pro-moted the differentiation of adipocyte-progenitors and 3T3-L1 *** array assay of CD45þimmune cells supernatant revealed that metalloproteinase inhibitor 1(TIMP1),an in-hibitor of adipogenesis,was reduced in Rarres2^(-/-)SAT,but increased in Rarres2^(-/-)*** we specifically knocked down chemerin in SAT,TIMP1 was down-regulated and adipogenesis was promoted with reducing infiltration of *** present study demonstrates that the effects of chemerin on adipose tissue is depot different,and specific knock down chemerin in SAT promote adipogenesis and improve glucose tolerance test(GTT)and insulin tolerance test(ITT).This suggests a potential therapeutic target for chemerin in the treatment of obesity related metabolic disorder.

关键词： Adipogenesis Adipose tissue depot chemerin Inflammation TIMP1

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chemerin Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production

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Current Medical Science 2023年第2期43卷 399-408页

作者： Shu-min KONG Xiao-yan SUN Wen-ya CUI Yu-chun CAO Department of Dermatology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Psoriasis is often combined with metabolic abnormalities,such as obesity and *** upregulation of chemerin,which is an essential protein produced primarily from white fat,is strongly correlated to the development of ***,there is no clarification on its exact function and mechanism in disease *** present study aims to determine its function and mechanism in disease *** The present study used a psoriasislike inflammatory cell model and imiquimod(IMQ)-induced mouse model to confirm whether chemerin is upregulated in psoriasis *** chemerin enhanced the keratinocyte proliferation,inflammatory cytokine secretion,and activation of the MAPK signaling ***,the intraperitoneal injection of neutralizing anti-chemerin antibody(ChAb)diminished the epidermal proliferation and inflammation in the IMQ-induced mouse *** The present results indicate that chemerin promotes keratinocyte proliferation,and enhances the production of inflammatory cytokines,thereby aggravating the ***,chemerin can be a prospective target for the treatment of psoriasis.

关键词： psoriasis keratinocyte chemerin proliferation inflammation

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chemerin is a key player in antimicrobial defense in skin

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Cellular & Molecular Immunology 2024年第6期21卷 638-640页

作者： Silvano Sozzani Francesca Sozio Annalisa Del Prete Department of Molecular Medicine Sapienza University of RomeLaboratory Affiliated to Institute Pasteur-ItaliaRomeItaly Department of Surgery Sapienza University of RomeRomeItaly Department of Molecular and Translational Medicine University of BresciaBresciaItaly IRCCS Humanitas Research Hospital RozzanoMilanItaly

The skin is the first line of defense to prevent entry of pathogenic bacteria from the environment and their dissemination to internal *** crucial function is accomplished mostly by keratinocytes,which serve as a phys... 详细信息

关键词： organs chemerin mostly

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Role of chemerin/CMKLR1 in the maintenance of earlypregnancy

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Frontiers of Medicine 2018年第5期12卷 525-532页

作者： Xuezhou Yang Junning Yao Qipeng Wei Jinhai Ye Xiaofang Yin Xiaozhen Quan Yanli Lan Hui Xing Department of Reproductive Medicine Center Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceXiangyang 441021 China Department of Reproductive Medicine Center Tongji Hospital Tongji Medical College Huazhong University ofScience and Technology Wuhan 430030 China

chemerin is a cytokine that attracts much attention in the reproductive process. This study aimed to explore the effects of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. The expression levels of chemerin and CMKLR1 in the decidua tissues of 20 early normal pregnant women and 20 early spontaneous abortion women were examined by Western blot and real-time polymerase chain reaction analyses. CMKLR1 receptor antagonist (α-NETA) was then intrauterinely injected into normal pregnant mice model to assess its effect on the outcome of pregnancy and the phosphorylation rate of ERK1/2 in decidua *** found that the expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy (P chemerin/CMKLR1 signaling pathway can lead to the abortion of mouse embryos, and that chemerin/CMKLR1 may play an important role in the maintenance of early pregnancy possibly by regulating ERK1/2 phosphorylation.

关键词： chemerin CMKLR1 early abortion

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Human chemerin induces eryptosis at concentrations exceeding circulating levels

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BIOCELL 2024年第8期48卷 1197-1208页

作者： MARYNA TKACHENKO ANATOLII ONISHCHENKO LILIYA TRYFONYUK DMYTRO BUTOV KATERYNA KOT VIKTORIIA NOVIKOVA LIWEI FAN VOLODYMYR PROKOPIUK YURII KOT ANTON TKACHENKO Department of Internal Medicine No.2 Clinical Immunology and AllergologyKharkiv National Medical UniversityKharkiv61022Ukraine Research Institute of Experimental and Clinical Medicine Kharkiv National Medical UniversityKharkiv61022Ukraine Institute of Health National University of Water and Environmental EngineeringRivne61022Ukraine Department of Infectious Diseases and Phthisiology Kharkiv National Medical UniversityKharkiv61022Ukraine Biochemistry Department V.N.Karazin Kharkiv National University Ministry of Education and Science of UkraineKharkiv61022Ukraine Department of Chemistry BiochemistryMicrobiology and Food HygieneState Biotechnological UniversityKharkiv61022Ukraine Clinical Research Innovation Lab Floor 26 Block D Qidi Technology Building 8Tsinghua Technology ParkBeijing100084China Department of Cryobiochemistry Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of UkraineKharkiv61015Ukraine

Introduction:Human chemerin is an adipokine that regulates chemotaxis,inflammation,and glucose *** addition,accumulating evidence suggests that chemerin promotes apoptosis,autophagy,and ***,there are no data on its impact on *** current study aimed to analyze the effects of human active Glu^(21)-Ser^(157) chemerin on eryptosis in *** and Methods:Human chemerin 0-2-10-50μg/mL was incubated for 24 h with human erythrocytes(hematocrit 0.4%)obtained from eight healthy *** cytometry-based determination of phospholipid scrambling,reactive oxygen species(ROS)production,and intracellular Ca^(2+)levels was *** supplement data on ROS and Ca^(2+)signaling in chemerin-mediated eryptosis,incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca^(2+)-binding agent EGTA was carried out,*** microscopy-based techniques were used to detect reactive nitrogen species(RNS)generation,involvement of caspase-3 and caspase-8,as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu^(21)-Ser^(157) ***:Our observations suggest that human Glu^(21)-Ser^(157) chemerin had no impact on eryptosis parameters at 2μg/***,chemerin stimulated phosphatidylserine externalization,ROS production,and Ca^(2+)accumulation at higher concentrations suggesting activation of ***^(2+)uptake turned out to be at least partly required for chemerin-mediated ***-mediated erythrotoxicity was additionally mediated by RNS,caspase-3,and ***,Glu^(21)-Ser^(157) chemerin promoted reduction in the liquid-ordered phase of cell membranes in ***:The present study first discloses that human chemerin can induce eryptosis via Ca^(2+)-dependent mechanisms at concentrations noticeably exceeding circulating ***,chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in disease

关键词： Adipokine Cell death chemerin Oxidative stress Eryptosis

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The level of chemerin and adipocyte fatty acid binding protein in Toxoplasma gondii seropositive obese individuals

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Asian Pacific Journal of Tropical Biomedicine 2017年第2期7卷 107-109页

作者： Agustin Iskandar Karomah Sriwedari Indah Adhita Wulanda Muhammad Rasjad Indra Hartojo Novi Khila Firani Ery Olivianto Department of Parasitology Medical Faculty of Universitas BrawijayaMalangEast JavaIndonesia Department of Clinical Pathology Medical Faculty of Universitas BrawijayaMalangEast JavaIndonesia Department of Physiology Medical Faculty of Universitas BrawijayaMalangEast JavaIndonesia Department of Biochemistry Medical Faculty of Universitas BrawijayaMalangEast JavaIndonesia Department of Child Health Medical Faculty of Universitas BrawijayaMalangEast JavaIndonesia

Objective: To know the difference between chemerin and adipocyte fatty acid-binding protein(AFABP) levels in obese individuals with positive Toxoplasma gondii(T. gondii)immunoglobulin G(IgG) compared with negative T. gondii ***: This study is a cross-sectional study by using consecutive sampling methods conducted from January to April 2013. The subjects were 57 obese individuals who were divided into obese group of positive and negative T. gondii IgG. The level of chemerin,AFABP and T. gondii IgG was done by ELISA. The data were analyzed by independent t ***: The results showed that the level of chemerin of positive T. gondii IgG group was significantly higher than the negative T. gondii IgG group [(70.0 ± 16.5) vs.(64.4 ± 16.1) pg/mL; P = 0.003], but there was not significant AFABP difference between seropositive and negative IgG groups [(83.6 ± 41.9) vs.(74.2 ± 36.7) pg/mL; P = 0.598].Conclusions: It can be concluded that the level of chemerin of seropositive T. gondii IgG was higher than that in the negative T. gondii IgG group.

关键词： chemerin AFABP Seropositive Toxoplasma gondii IgG Obese

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CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis

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Fundamental Research 2024年第3期4卷 575-588页

作者： Zewei Zhao Siqi Liu Bingxiu Qian Lin Zhou Jianglin Shi Junxi Liu Lin Xu Zhonghan Yang Department of Biochemistry Molecular Cancer Research CenterSchool of MedicineSun Yat-sen UniversityShenzhenGuangdong 518107China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Public Health Sun Yat-sen UniversityGuangzhouGuangdong 510080China

Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in ***,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical *** study aimed at identifying a potential GPCR target to induce beige *** found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat ***,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat ***,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling *** further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of *** conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

关键词： Obesity Insulin resistance Thermogenesis CMKLR1 Resolvin E1 chemerin

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Association of Serum chemerin Levels with Coronary Artery Disease: Pathogenesis and Clinical Research

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Cardiovascular Innovations and Applications 2020年第2期4卷 251-256页

作者： Lutfu Askin Hakan Duman Ali Ozyıldız Okan Tanriverdi Department of Cardiology Adiyaman Education and Research HospitalAdiyamanTurkey Department of Cardiology Faculty of MedicineRecep Tayyip Erdogan UniversityRizeTurkey

Recent studies have revealed that chemerin plays an essential role in the development of cardiovascular *** studies found a strong correlation between the secretion of chemerin in peripheral tissues and aortic and coronary *** chemerin is a marker of systemic infl ammation and is associated with metabolic *** plays a vital role in vascular infl ammation and *** chemerin levels are increased in patients with dilated cardiomyopathy,and chemerin is associated with left ventricular *** this review,we focus on chemerin expression,chemerin processing,its biological function,and its role in the diagnosis of cardiovascular diseases.

关键词： atherosclerosis chemerin heart failure coronary artery disease infl ammation metabolic syndrome

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Biphasic modulation of chemerin peptide-induced calcium flux and ERK phosphorylation by amyloid beta peptide

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中国药理学与毒理学杂志 2017年第10期31卷 1020-1021页

作者： Hao GONG Shuo ZHANG Dan LIAO Richard Dequan YE School of Pharmacy Shanghai Jiao Tong University Institute of Chinese Medical Sciences University of Macao

OBJECTIVE The chemokine-like receptor 1(CMKLR1,Chem R23) is a functional receptor for chemerin,the chemerin-derived nonapeptide(C9),and the amyloid β peptide 1-42(Aβ_(42)).Because these peptides share little sequence homology,studies were conducted to investigate their pharmacological properties and regulation at *** Cells expressing CMKLR1 were incubated with Aβ_(42) before stimulation with a strong agonist,the C9 *** mobilization,c AMP inhibition and MAP kinase activation were *** FRET were determined using CMKLR1 constructs with an ECFP attached to the C-terminus and a Fl As H binding motif embedded in the first intracellular loop(IL1).RESULTS Binding of both Aβ_(42) and the C9 peptide induced CMKLR1 internalization,but only the Aβ_(42)-induced receptor internalization involved clathrin-coated ***,Aβ_(42) but not C9 stimulated β-arrestin 2 translocation to plasma membranes.A robust Ca^(2+)flux was observed following C9 stimulation,whereas Aβ_(42) was ineffective even at micromolar *** its low potency in calcium mobilization assay,Aβ_(42) was able to alter C9-induced Ca^(2+) flux in dose-dependent manner:a potentiation effect at 100 pmol·L^(-1) of Aβ_(42) was followed by a suppression at 10 nmol·L^(-1) and further potentiation at 1 μmol·L^(-1).This unusual and biphasic modulatory effect was also seen in the C9-induced ERK phosphorylation but the dose curve was opposite to that of Ca^(2+) flux and c AMP inhibition,suggesting a reciprocal regulatory *** FRET assay confirmed that Aβ_(42) modulates CMKLR1 rather than its downstream signaling *** These findings suggest Aβ_(42) as an allosteric modulator that can both positively and negatively regulate the activation state of CMKLR1 in a manner that differs from existing allosteric modulatory mechanisms.

关键词： G protein-coupled receptors allosteric modulation fluorescent resonance energy transfer chemokine like receptor 1 chemerin conformational changes

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