Chemerin Expression Research Articles

Association of chemerin mRNA expression in human epicardial adipose tissue with coronary atherosclerosis

BackgroundGrowing evidence suggests that epicardial adipose tissue (EAT) may play a key role in the pathogenesis and development of coronary artery disease (CAD) by producing several inflammatory adipokines. Chemerin, a novel adipokine, has been reported to be involved in regulating immune responses and glucolipid metabolism. Given these properties, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis. In this study, we sought to determine the relationship of chemerin expression in EAT and the severity of coronary atherosclerosis in Han Chinese patients.MethodsSerums and adipose tissue biopsies (epicardial and thoracic subcutaneous) were obtained from CAD (n = 37) and NCAD (n = 16) patients undergoing elective cardiac surgery. Gensini score was used to assess the severity of CAD. Serum levels of chemerin, adiponectin and insulin were measured by ELISA. Chemerin protein expression in adipose tissue was detected by immunohistochemistry. The mRNA levels of chemerin, chemR23, adiponectin and TNF-alpha in adipose tissue were detected by RT-PCR.ResultsWe found that EAT of CAD group showed significantly higher levels of chemerin and TNF-alpha mRNA, and significantly lower level of adiponectin mRNA than that of NCAD patients. In CAD group, significantly higher levels of chemerin mRNA and protein were observed in EAT than in paired subcutaneous adipose tissue (SAT), whereas such significant difference was not found in NCAD group. Chemerin mRNA expression in EAT was positively correlated with Gensini score (r = 0.365, P < 0.05), moreover, this correlation remained statistically significant (r = 0.357, P < 0.05) after adjusting for age, gender, BMI and waist circumference. Chemerin mRNA expression in EAT was also positively correlated with BMI (r = 0.305, P < 0.05), waist circumference (r = 0.384, P < 0.01), fasting blood glucose (r = 0.334, P < 0.05) and negatively correlated with adiponectin mRNA expression in EAT (r = -0.322, P < 0.05). However, there were no significant differences in the serum levels of chemerin or adiponectin between the two groups. Likewise, neither serum chemerin nor serum adiponectin was associated with Gensini score (P > 0.05).ConclusionsThe expressions of chemerin mRNA and protein are significantly higher in EAT from patients with CAD in Han Chinese patients. Furthermore, the severity of coronary atherosclerosis is positive correlated with the level of chemerin mRNA in EAT rather than its circulating level.

Expression of Chemerin Correlates With a Favorable Prognosis in Patients With Non-Small Cell Lung Cancer

Chemerin was shown to play a role in the colocalization of natural killer (NK) cells, which have an antitumor role. We aimed to determine the expression of chemerin and the relationship of chemerin expression with prognosis in patients with non-small cell lung cancer (NSCLC). We examined chemerin expression and the infiltration number of NK cells in NSCLC patients using immunohistochemistry. The association of chemerin expression with clinicopathologic characteristics and prognosis was analyzed. Of the NSCLC patients, 51.85% exhibited lower expression levels of chemerin protein. The chemerin expression was significantly correlated with histological grade and the infiltration of NK cells. Non-small cell lung cancer patients with a lower chemerin expression had poorer survival rates than those with a higher expression. Multi-variable Cox regression analysis revealed that the chemerin expression level was an independent factor for prognosis. A greater expression of chemerin is an independent predictor of a better prognosis for patients with NSCLC.

Chemerin, a Novel Peroxisome Proliferator-activated Receptor γ (PPARγ) Target Gene That Promotes Mesenchymal Stem Cell Adipogenesis

Chemerin is an adipocyte-secreted protein that regulates adipogenesis and the metabolic function of mature adipocytes via activation of chemokine-like receptor 1 (CMKLR1). Herein we report the interaction of peroxisome proliferator-activated receptor γ (PPARγ) and chemerin in the context of adipogenesis. Knockdown of chemerin or CMKLR1 expression or antibody neutralization of secreted chemerin protein arrested adipogenic clonal expansion of bone marrow mesenchymal stem cells (BMSCs) by inducing a loss of G(2)/M cyclins (cyclin A2/B2) but not the G(1)/S cyclin D2. Forced expression of PPARγ in BMSCs did not completely rescue this loss of clonal expansion and adipogenesis following chemerin or CMKLR1 knockdown. However, forced expression and/or activation of PPARγ in BMSCs as well as non-adipogenic cell types such as NIH-3T3 embryonic fibroblasts and MCA38 colon carcinoma cells significantly induced chemerin expression and secretion. Sequence analysis revealed a putative PPARγ response element (PPRE) sequence within the chemerin promoter. This PPRE was able to confer PPARγ responsiveness on a heterologous promoter, and mutation of this sequence abolished activation of the chemerin promoter by PPARγ. Chromatin immunoprecipitation confirmed the direct association of PPARγ with this PPRE. Treatment of mice with rosiglitazone elevated chemerin mRNA levels in adipose tissue and bone marrow coincident with an increase in circulating chemerin levels. Together, these findings support a fundamental role for chemerin/CMKLR1 signaling in clonal expansion during adipocyte differentiation as well as a role for PPARγ in regulating chemerin expression.

Molecular cloning, tissue distribution and ontogenetic expression of Xiang pig Chemerin and its involvement in regulating energy metabolism through Akt and ERK1/2 signaling pathways

Chemerin, as a new member of adipokines family, is highly expressed in adipose tissue in rodent and its expression increases with obesity. Moreover, chemerin has been reported to have significant relationship with metabolic syndrome and insulin sensitivity. Here, the gene encoding chemerin from Xiang pig was cloned. The open reading frame of this cDNA encodes 163 deduced amino acid residues. The putative protein has a N-terminal signaling peptide and a nuclear localization signal profile which are highly conserved among the vertebrate orthologs. Both chemerin and chemerinR are highly expressed in lung, kidney and small intestine in adult Xiang pig. Besides these tissues, chemerin is abundant in liver and backfat, and chemerinR is abundant in spleen and skeletal muscle. We also investigated the age-dependent expression of chemerin in suckling Xiang piglets in various tissues, which showed an interaction between age and segments in abundance of chemerin and chemerinR from day 1 to day 21. For chemerinR, it was abundant in skeletal muscle of both adult and fetal Xiang pig. Further, we treated differentiated C2C12 cells with chemerin. The result showed that chemerin regulated energy metabolism partly through Akt and ERK1/2 signaling pathway. Taken together, our findings provide basic molecular information for the deeper investigation on the function of chemerin.

TNFα and chemerin cross-talk in rheumatoid arthritis

Background and objectivesRheumatoid arthritis (RA) synovium is characterised by a dense infiltrate, consisting of macrophages, T and B cells, plasma cells and dendritic cells (DC). Inflammatory chemokines present in RA...

Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes

BackgroundObesity is a major risk factor for a plethora of diseases including joint disorders associated with cartilage destruction. Recently, it has been demonstrated that adipose tissue might contribute to degenerative...

Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis

IntroductionChemerin is a chemotactic agonist identified as a ligand for ChemR23 that is expressed on macrophages and dendritic cells (DCs). In this study, we analyzed the expression of chemerin and ChemR23 in the synovium of rheumatoid arthritis (RA) patients and the stimulatory effects of chemerin on fibroblast-like synoviocytes (FLSs) from RA patients.MethodsChemerin and ChemR23 expression in the RA synovium was ascertained by immunohistochemistry and Western blot analysis. Chemerin expression on cultured FLSs was analyzed by ELISA. ChemR23 expression on FLSs was determined by immunocytochemistry and Western blot analysis. Cytokine production from FLSs was measured by ELISA. FLS cell motility was evaluated by utilizing a scrape motility assay. We also examined the stimulating effect of chemerin on the phosphorylation of mitogen-activated protein kinase (MAPK), p44/42 mitogen-activated protein kinase (ERK1/2), p38MAPK, c-Jun N-terminal kinase (JNK)1/2 and Akt, as well as on the degradation of regulator of NF-κB (IκBα) in FLSs, by Western blot analysis.ResultsChemerin was expressed on endothelial cells and synovial lining and sublining cells. ChemR23 was expressed on macrophages, immature DCs and FLSs and a few mature DCs in the RA synovium. Chemerin and ChemR23 were highly expressed in the RA synovium compared with osteoarthritis. Chemerin and ChemR23 were expressed on unstimulated FLSs. TNF-α and IFN-γ upregulated chemerin production. Chemerin enhanced the production of IL-6, chemokine (C-C motif) ligand 2 and matrix metalloproteinase 3 by FLSs, as well as increasing FLS motility. The stimulatory effects of chemerin on FLSs were mediated by activation of ERK1/2, p38MAPK and Akt, but not by JNK1/2. Degradation of IκB in FLSs was not promoted by chemerin stimulation. Inhibition of the ERK1/2, p38MAPK and Akt signaling pathways significantly suppressed chemerin-induced IL-6 production. Moreover, blockade of the p38MAPK and Akt pathways, but not the ERK1/2 pathway, inhibited chemerin-enhanced cell motility.ConclusionsThe interaction of chemerin and ChemR23 may play an important role in the pathogenesis of RA through the activation of FLSs.

Chemerin: A Novel Link between Inflammation and Atherosclerosis?

Chemerin: A Novel Link between Inflammation and Atherosclerosis?

Expression of Human Chemerin Induces Insulin Resistance in the Skeletal Muscle but Does Not Affect Weight, Lipid Levels, and Atherosclerosis in LDL Receptor Knockout Mice on High-Fat Diet

OBJECTIVEChemerin is a recently discovered hepatoadipokine that regulates adipocyte differentiation as well as chemotaxis and activation of dendritic cells and macrophages. Chemerin was reported to modulate insulin sensitivity in adipocytes and skeletal muscle cells in vitro and to exacerbate glucose intolerance in several mouse models in vivo. In humans, chemerin was shown to be associated with multiple components of the metabolic syndrome including BMI, triglycerides, HDL cholesterol, and hypertension. This study aimed to examine the effect of chemerin on weight, glucose and lipid metabolism, as well as atherosclerosis in vivo.RESEARCH DESIGN AND METHODSWe used recombinant adeno-associated virus to express human chemerin in LDL receptor knockout mice on high-fat diet.RESULTSExpression of chemerin did not significantly alter weight, lipid levels, and extent of atherosclerosis. Chemerin, however, significantly increased glucose levels during the intraperitoneal glucose tolerance test without affecting endogenous insulin levels and the insulin tolerance test. Chemerin reduced insulin-stimulated Akt1 phosphorylation and activation of 5′AMP-activated protein kinase (AMPK) in the skeletal muscle, but had no effect on Akt phosphorylation and insulin-stimulated AMPK activation in the liver and gonadal adipose tissue.CONCLUSIONSChemerin induces insulin resistance in the skeletal muscle in vivo. Chemerin is involved in the cross talk between liver, adipose tissue, and skeletal muscle.

The expression of chemerin and chemerin receptor in rats with methionine-and choline-deficient diet induced nonalcoholic fatty liver disease

Objective To explore the expression of chemerin and chemerin receptor ( chemokine-like receptor 1, CMKLR1) during different periods of non-alcoholic fatty liver disease ( NAFLD) rat model induced by methionine- and choline-deficient ( MCD) diet. Methods Thirty-six Wistar rats were divided into control group and MCD group in random. After one week quarantine and acclimation period, these two groups were fed either normal chow or MCD diet. The animals were respectively sacrificed at the first week, the forth week, and the tenth week. The levels of alanine transaminase (ALT), blood lipid profile, liver function, and the content of triglyceride in liver were detected. HE staining was done to observe the morphologic change of liver. The mRNA expression changes of chemerin and CMKLR1 in liver were measured using real-time PCR, and the change in chemerin mRNA level was further confirmed in liver by Northern blot. Finally, the concentration of chemerin in serum was measured by Western blot. Results The mRNA level of chemerin decreased significantly after four and ten weeks MCD feeding, although no obvious changes were found at first week, similar changes were found in serum chemerin (1.00±0.11 vs 0.96±0.39; 1.00±0.12 vs 0.21 ±0.77; 1.00±0.42 vs 0.21 ±0. 11). Contrasting with the change of chemerin(1.00±0.08 vs 0.72±0.10;1.00±0.24 vs 0.63±0. 31 ;1.00±0.05 vs 0.50±0.13), the mRNA level of CMKLR1 increased after MCD feeding( 1.00±0. 14 vs 0. 84±0. 26; 1.00±0. 38 vs 1. 51 ±0. 33; 1. 01 ±0. 13 vs 1. 84 ± 0. 39 ). Conclusion The change of chemerin and its receptor may participate in the process of the nonalcoholic fatty liver disease. Key words: Methionine- and choline-deficient diet; Chemerin; CMKLR1; Nonalcoholic fatty liver disease

Abstract 2939: Leukocyte chemoattractant chemerin as a novel immunotherapeutic agent

Abstract Cancer immunotherapy offers the potential of potent anti-tumor responses while avoiding non-specific toxicities associated with traditional cytotoxic chemotherapy. Localization of key immune cells to tumor sites has been shown to be important for anti-tumor efficacy. Chemerin is a recently described chemoattractant initially isolated from human inflammatory fluids. Chemokine-like receptor 1 (CMKLR1) constitutes the main cellular receptor for chemerin, and is expressed by macrophages, natural killer (NK) cells, and immature dendritic cells (DCs), but has not been shown on T lymphocytes. Chemerin is synthesized and circulates systemically as an inactive precursor, prochemerin, but can be rapidly converted into its active form by proteolytic cleavage of carboxy-terminal residues by multiple proteases. To evaluate chemerin as a potential immunotherapy, we performed intratumoral injections of recombinant active murine chemerin that resulted in significantly decreased tumor growth in a B16 melanoma as well as JC breast tumor models. Tumors lines showed no expression of CMKLR1 by flow cytometric (FACS) analysis, and treatment with exogenous recombinant murine chemerin had no effect on in vitro proliferation. Compared to control media, B16 tumor-conditioned serum-free media was able to attract CMKLR1-transfected L1.2 cells (L1.2/CMKLR1) after the addition of inactive, recombinant murine prochemerin, indicating the ability of tumor-derived factors to activate prochemerin. Treatment with the pan-matrix metalloproteinase (MMP) inhibitor GM6001 resulted in reduced chemotaxis, suggesting the activation of chemerin was in part mediated by MMPs. This supports the ability of tumors to activate prochemerin. B16, as well as additional mouse tumor lines (JC, CT26, EMT6), were then transfected to constitutively express chemerin. Experiments using all tumor lines showed consistent and significantly decreased growth of chemerin-expressing tumors compared with control tumors. There were greater numbers of leukocytes in both the tumors and draining lymph nodes compared to controls. CMKLR1 knockout mice we generated showed abrogated response to chemerin-expressing tumors, supporting the hypothesis that the anti-tumor effects are mediated by this receptor. CD4 and CD8 T lymphocytes from tumor-bearing mice were isolated and shown, for the first time, to have significant CMKLR1 expression compared to control lymphocytes from naïve mice. Incubation of naïve T cells with tumor-conditioned media recapitulated these results, suggesting CMKLR1 expression can be induced by tumor-derived factors. These data suggest not only that tumor-derived proteases can activate chemerin, but also that chemerin expression at tumor sites results in the recruitment of CMKLR1-positive cells, potentially including CMKLR1+ lymphocytes, and establishment of an effective anti-tumor immune response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2939.

Possible functional roles of chemerin, a new adipokine, in domestic animals

Chemerin was recently identified as a novel adipokine highly expressed in adipose tissues of mouse and human and suggested to play a role in the pathophysiology of obesity. However, the function roles of chemerin in metabolic and cellular processes in domestic animals still remain unknown. Full‐length cDNA and predicted amino acid sequences of bovine chemerin and chemerin receptor were found to be highly homologous to those of the human and mouse, suggesting similar functions of these genes in cattle as in other species. Bovine chemerin mRNA was highly expressed in adipose tissues and liver, and the transcripts of chemerin receptor was abundant in adipose tissues, muscle, liver and brain. Both transcripts of chemerin and chemerin receptor were up‐regulated during the adipocyte differentiation of bovine preadipocytes. TNF‐ƒ¿ treatment (10ng/ml), an inhibitor of adipocyte differentiation, in bovine differentiated adipocytes increased the mRNA expression of bovine chemerin and chemerin receptor. These results indicate that chemerin, highly expressed in adipose tissues, regulate the fatty metabolism in adipose tissue through its receptor in cattle.

Cloning, expression analysis, and regulatory mechanisms of bovine chemerin and chemerin receptor

Recently, we reported that chemerin, a new adipokine, is highly expressed in the adipose tissue, up-regulated during adipocyte differentiation, and regulates adipogenesis via its own receptor in mice. The objectives of this study were to clone chemerin and its receptor from the adipose tissues of Japanese Black cattle and to investigate the expression of these genes in 16 different tissues. We compared the gene expression of chemerin and its receptor between adipocytes and stromal-vascular (S-V) cells (non-adipocytes) prepared from subcutaneous adipose tissue. In addition, we investigated the mRNA expression levels of chemerin and its receptor in bovine differentiated adipocytes. The DNA sequences of bovine chemerin and its receptor were determined, and they were found to be highly homologous to those of humans, mice, and pigs. The amino acid sequences predicted for the full-length cDNA of bovine chemerin and its receptor were also similar to those of humans, mice, and pigs, suggesting that these genes have similar functions. Bovine chemerin mRNA was highly expressed in the adipose and liver tissues, and the transcripts of chemerin receptor were widely expressed in several tissues including adipose, muscle, liver, and brain tissues. The expression of bovine chemerin mRNA was higher in adipocytes than in S-V cells prepared from adipose tissue. The transcripts of chemerin and its receptor were up-regulated during adipocyte differentiation. Treatment with tumor necrosis factor (TNF)-α (10 ng/mL) in bovine differentiated adipocytes increased the mRNA expression of chemerin and its receptor. These results indicate that chemerin, a new adipokine highly expressed in the adipocytes of bovine adipose tissue, is the TNF-α-up-regulated gene with a role in adipogenesis.

Chemerin Exacerbates Glucose Intolerance in Mouse Models of Obesity and Diabetes

Obesity, characterized by an excess of adipose tissue, is an established risk factor for cardiovascular disease and type 2 diabetes. Different mechanisms linking obesity with these comorbidities have been postulated but remain poorly understood. Adipose tissue secretes a number of hormone-like compounds, termed adipokines, that are important for the maintenance of normal glucose metabolism. Alterations in the secretion of adipokines with obesity are believed to contribute to the undesirable changes in glucose metabolism that ultimately result in the development of type 2 diabetes. In the present study, we have shown that serum levels of the novel adipokine chemerin are significantly elevated in mouse models of obesity/diabetes. The expression of chemerin and its receptors, chemokine-like receptor 1, chemokine (C-C motif) receptor-like 2, and G protein-coupled receptor 1 are altered in white adipose, skeletal muscle, and liver tissue of obese/diabetic mice. Administration of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. Collectively, these data indicate that chemerin influences glucose homeostasis and may contribute to the metabolic derangements characteristic of obesity and type 2 diabetes.

Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells

Maintenance of healthy bone mass requires a well-coordinated balance between the ongoing processes of bone formation and bone resorption. Bone-forming osteoblasts derive from resident adult stem cells within bone marrow called bone marrow stromal cells (BMSCs). These BMSCs are multipotent and also can give rise to adipocytes, which do not contribute directly to bone formation but may influence bone remodeling through the release of bioactive signaling molecules. Chemerin is a novel adipocyte-derived signaling molecule that promotes adipocyte differentiation. In this study we examined the role of chemerin and the cognate receptors CMKLR1 and CCRL2 as determinants of osteoblast and adipocyte differentiation of the preosteoblast 7F2 cell line and of primary BMSCs. Expression and secretion of chemerin increased dramatically with adipocyte differentiation of these cells. Functionally, knockdown of chemerin or CMKLR1 expression using RNA interference abrogated adipocyte differentiation, clonal expansion, and basal proliferation of BMSCs. In contrast, knockdown of either gene was associated with increased osteoblast marker gene expression and mineralization in response to osteoblastogenic stimuli. Forced expression of the adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) induced chemerin expression and partially rescued the loss of adipogenesis associated with chemerin or CMKLR1 knockdown in BMSCs. Taken together, these data support a novel role for chemerin/CMKLR1 signaling in regulating adipogenesis and osteoblastogenesis of bone marrow-derived precursor cells. These data reveal a potential role for this signaling pathway as a modulator of bone mass.

Adipokines in Periaortic and Epicardial Adipose Tissue: Differential Expression and Relation to Atherosclerosis

Adipokines are protein products of adipose tissue with paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis. Standard immunohistochemical staining for the adipokines was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification. Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated with atherosclerosis. Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin21-157

IntroductionChemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators.MethodsTissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin21-157. Biological effects of chemerin21-157 were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants.ResultsBoth serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin21-157 resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected.ConclusionsThese results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin21-157 stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation.

Detection of Chemerin and It's Clinical Significance in Peripheral Blood of Patients with Lung Cancer.

Chemerin was recently found a chemoattractant just like a chemotatic factor. It can induce immune chemotaxis to dendritic cells and macrophages by binding to its receptor ChemR23. It has been known that the activation of Chemerin could enhance the phagocytosis and antigen presentation of APC. Along with this observation, the contribution of Chemerin in the genesis and development of a tumor attracts more attention. We explored the relation between Chemerin and lung cancer through detecting the expression of Chemerin in peripheral blood of patients. The experiment selected samples of lung cancer patients and normal people. The concentration of Chemerin in peripheral blood was detected by ELISA method. T test was used to compare the statistic difference. We compared the concentration of Chemerin in peripheral blood with age, sex, pathological type, degree of differentiation, metastasis of lymphonode, UICC staging and other clinicopathological index, and analyzed by t test and one-way ANOVA. The concentration of Chemerin in peripheral blood of 42 patients with lung cancer (1 965.81 pg/mL+/-374.03 pg/mL) were significantly higher than the concentration of 31 healthy examination (1 111.44 pg/mL+/-250.72 pg/mL)(P<0.001). The concentration of Chemerin in peripheral blood of patients with lung cancer had no relationship with clinicopathological factors. Chemerin has the potential to lung cancer diagnosis as a marker.

Expressions and purification of a mature form of recombinant human Chemerin in Escherichia coli

Chemerin is a novel chemokine that binds to the G protein-coupled receptor (GPCR) ChemR23, also known as chemokine-like receptor 1 (CMKLR1). It is secreted as a precursor and executes pro-inflammatory functions when the last six amino acids are removed from its C-terminus by serine proteases. After maturation, Chemerin attracts dendritic cells and macrophages through binding to ChemR23. We report a new method for expression and purification of mature recombinant human Chemerin (rhChemerin) using a prokaryotic system. After being expressed in bacteria, rhChemerin in inclusion bodies was denatured using 6 M guanidine chloride. Soluble rhChemerin was prepared by the protein-specific renaturation solution under defined conditions. It was subsequently purified using ion-exchange columns to more than 95% purity with endotoxin level <1.0 EU/μg. We further demonstrated its biological activities for attracting migration of human dendritic cells and murine macrophages in vitro using established chemotaxis assays.

Insulin and Metformin Regulate Circulating and Adipose Tissue Chemerin

OBJECTIVETo assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects.RESEARCH DESIGN AND METHODSReal-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzyme-linked immunosorbent assay. We investigated the in vivo effects of insulin on serum chemerin levels via a prolonged insulin-glucose infusion. Ex vivo effects of insulin, metformin, and steroid hormones on adipose tissue chemerin protein production and secretion into conditioned media were assessed by Western blotting and enzyme-linked immunosorbent assay, respectively.RESULTSSerum chemerin, subcutaneous, and omental adipose tissue chemerin were significantly higher in women with PCOS (n = 14; P < 0.05, P < 0.01). Hyperinsulinemic induction in human subjects significantly increased serum chemerin levels (n = 6; P < 0.05, P < 0.01). In adipose tissue explants, insulin significantly increased (n = 6; P < 0.05, P < 0.01) whereas metformin significantly decreased (n = 6; P < 0.05, P < 0.01) chemerin protein production and secretion into conditioned media, respectively. After 6 months of metformin treatment, there was a significant decrease in serum chemerin (n = 21; P < 0.01). Importantly, changes in homeostasis model assessment–insulin resistance were predictive of changes in serum chemerin (P = 0.046).CONCLUSIONSSerum and adipose tissue chemerin levels are increased in women with PCOS and are upregulated by insulin. Metformin treatment decreases serum chemerin in these women.