Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin a1 in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice / 神经科学通报·英文版

A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation / 中华微生物学和免疫学杂志

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Research advances of chemokine receptor CX3CR1 and microglia in retinal degenerative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration are the main clinical blinding eye diseases with complex etiology and irreversible damage to vision. CX3CR1 is a specific receptor of the chemokine CX3CL1. Both of them participate in various physiological functions and pathological changes of the whole body through regulating the immune system of the body. In recent years, studies have pointed out that CX3CR1 regulates the activity and function of retinal microglia, which play an important role in the process of retinal degenerative diseases. In this paper, the structure and function of the chemokine receptor CX3CR1 and the role of microglia in retinal degenerative diseases were reviewed, so as to provide ideas and directions for future research and treatment of such diseases.

Involvement of NF-κB and the CX3CR1 Signaling Network in Mechanical Allodynia Induced by Tetanic Sciatic Stimulation / 神经科学通报·英文版

Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test. The expression of phosphorylated NF-κB (pNF-κB) and CX3CR1 was significantly up-regulated in the bilateral dorsal horn. Immunofluorescence staining demonstrated that pNF-κB and NeuN co-existed, implying that the NF-κB pathway is predominantly activated in neurons following TSS. Administration of either the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate or a CX3CR1-neutralizing antibody blocked the development and maintenance of neuropathic pain. In addition, blockade of NF-κB down-regulated the expression of CX3CL1-CX3CR1 signaling, and conversely the CX3CR1-neutralizing antibody also down-regulated pNF-κB. These findings suggest an involvement of NF-κB and the CX3CR1 signaling network in the development and maintenance of TSS-induced mechanical allodynia. Our work suggests the potential clinical application of NF-κB inhibitors or CX3CR1-neutralizing antibodies in treating pathological pain.

The clinical characteristics of de novo primary AML with higher blast cell ratio in peripheral blood than bone marrow and its e relationship with CR1 / 实用医学杂志

Objective To analyze the clinical characteristics of de novo primary AML patients with higher blast cell ratio in peripheral blood than bone marrow and its relationship with CR1. Methods The clinical data on de novo primary AML patients in Henan Provincial Tumor Hospital from January 2015 to December 2016 were ret-rospectively reviewed. Based on the proportion of blast cells in the peripheral blood and bone marrow ,the patients were divided into BHG and NBHG. All the data was analyzed respectively by Schisquare test ,rank sum test or Spearman correlation analysis according to the types of clinical data. Results As compared with NBHG patients , BHG patients had a higher rate of bleeding,palpitation,M2 subtype,FLT3-ITD mutation,and average level of LDH andα-HBDH in serum before treatment,and the difference was statistically significant(P<0.05);however, the rate of CR1,M3 and M5 subtype in BHG patients was lower than that in NBHG patients,and the difference was statistically significant(P < 0.05). The proportion of peripheral blood blast cells in patients with AML has a positive correlation with serum levels of LDH and α-HBDH(R:0.331 and 0.352,P < 0.05). Conclusions De novo primary AML patients with higher blast cell ratio in peripheral blood than bone marrow are mostly M2 subtype,easily associated with FLT3-ITD mutation,bleeding and palpitation symptoms,and they have a lower CR1rate. The proportion of blast cells in peripheral blood is positively correlated with levels of serum LDH and α-HBDH.

Effects of Xueniaoan Tablets on Complement Regulatory Protein CR1 in IgA Nephropathy Rats / 中国药师

Objective:To observe the effect of Xueniaoan tablets on the expression of complement regulatory protein CR1 in IgA nephropathy rats. Methods:Totally 36 SD rats were randomized into the normal group,the model group and Xueniaoan group after 4-day adaptive feeding. Complex method was used to establish IgA nephropathy model,and Xueniaoan group was given Xueniaoan at the dose of 7.0 g·kg-1during the 10thweek and the 12thweek,while the normal group and the model group were fed with normal saline, and the administration course was 3 weeks. The 24-h urine protein was detected,CR1 in red blood cells was detected by ELISA,the renal pathological changes were observed under a light microscope after HE staining,and the expression of CR1 was detected by immu-nohistochemistry. Results:Compared with that in the model group,the 24-h proteinuria in Xueniaoan group was significantly reduced, the number of red blood cell CR1 increased significantly (P<0.05), CR1 in renal tissue increased and the renal tissue injury was light. Conclusion:Xueniaoan tablets can delay the renal damages in IgA nephropathy rats through promoting the expression of CR1.

Role of spinal CX3CR1 in inflammatory pain in mice:the relationship with CaM-CaMKⅡ signaling pathways / 中华麻醉学杂志

Objective To evaluate the role of spinal CX3C chemokine receptor 1 (CX3CR1) in inflammatory pain and the relationship with calmodulin (CaM)-calmodulin-dependent protein kinaseⅡ(CaMKⅡ) signaling pathways in mice.Methods Ninety-six pathogen-free healthy male C57BL6 mice,weighing 25-27 g,were divided into 3 groups using a random number table:control group (group C,n=30),inflammatory pain group (group IP,n=36) and CX3CR1 antagonist group (group CA,n=30).Inflammatory pain was induced by injecting complete Freund′s adjuvant (CFA) 50 μl into the plantar surface of right hind paws in IP and CA groups,while the equal volume of normal saline was given instead in group C.In group CA,CX3CR1 antagonist (diluted to 1 μg/5 μl in phosphate buffer solution) was intrathecally injected at 1 h before CFA injection.The thermal paw withdrawal latency (TWL) was measured at 30 min before CFA injection (T0) and 30 min,1 h,2 h and 4 h after CFA injection (T2-4).The animals were then sacrificed,and the spinal cord was removed for determination of the expression of phosphorylated CaMKⅡ (p-CaMKⅡ),phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) and c-fos (by Western blot) and expression of CaMKⅡ,CREB and c-fos mRNA (using real-time polymerase chain reaction).Immunofluorescence was used to determine that p-CAMKⅡ was expressed in microglia.Results Compared with group C,the TWL was significantly shortened at T2-4,and the expression of p-CaMKⅡ,p-CREB and c-fos protein and mRNA was up-regulated at T1-4 in IP and CA groups (P<0.05).Compared with group IP,the TWL was significantly prolonged at T2-4,and the expression of p-CaMKⅡ,p-CREB and c-fos protein and mRNA was down-regulated at T1-4 in group CA (P<0.05).p-CaMKⅡ was co-expressed with the microglial specific biomarker.Conclusion CX3CR1 is involved in the development and maintenance of inflammatory pain through activating CaM-CaMKⅡsignaling pathways in mice.

Complement and membrane-bound complement regulatory proteins as biomarkers and therapeutic targets for autoimmune inflammatory disorders, RA and SLE.

Complement system is a major effecter system of the innate immunity that bridges with adaptive immunity. The system consists of about 40 humoral and cell surface proteins that include zymogens, receptors and regulators. The zymogens get activated in a cascade fashion by antigen-antibody complex, antigen alone or by polymannans, respectively, by the classical, alternative and mannose binding lectin (MBL) pathways. The ongoing research on complement regulators and complement receptors suggest key role of these proteins in the initiation, regulation and effecter mechanisms of the innate and adaptive immunity. Although, the complement system provides the first line of defence against the invading pathogens, its aberrant uncontrolled activation causes extensive self tissue injury. A large number of humoral and cell surface complement regulatory protein keep the system well-regulated in healthy individuals. Complement profiling had brought important information on the pathophysiology of several infectious and chronic inflammatory disorders. In view of the diversity of the clinical disorders involving abnormal complement activity or regulation, which include both acute and chronic diseases that affect a wide range of organs, diverse yet specifically tailored therapeutic approaches may be needed to shift complement back into balance. This brief review discusses on the complement system, its functions and its importance as biomarkers and therapeutic targets for autoimmune diseases with focus on SLE and RA.

Effect of shenqifuzheng injection on CX3CR1 in colonic mucosa of patients with ulcerative colitis / 重庆医学

Objective To observe the clinical efficacy of shenqifuzheng injection combined with sulfasalazine (SASP) in the treatment of ulcerative colitis (UC) ,and to evaluate the effect of CX3CR1 on colonic mucosa of UC in treatment with shenqifuzheng injection .Methods Fifty‐one patients with active mild to moderate UC were collected during the period from January 2012 to June 2014 in the second people′s hospital of Lianyungang ,which randomly divided into experimental group and control group ,and setting up health group of 15 cases .Experimental group were treated with shenqifuzheng injection combined with SASP ,control group were only with SASP ,health group were no‐treatment control .The modified Mayo scoring results and the expression of CX3CR1 on co‐lonic mucosa of the same lesion site were observed before and two weeks after treatment separately .Results The total positive rate of CX3CR1 on colonic mucosa in patients with ulcerative colitis was 88 .37% before treatment ,The total positive rate of CX3CR1 on colonic mucosa in health group was 20 .00% ,There was significant difference between two groups (Z= -2 .689 ,P<0 .01) .Two weeks after treatment ,the expression of CX3CR1 on colonic mucosa and the modified Mayo scoring results in the experimental group were significantly lower than those in the control group (P<0 .05) .The clinical comprehensive efficacy of the experimental group was significantly better than the control group (Z= -2 .085 ,P<0 .05) .Conclusion Combination of shenqifuzheng injection and SASP is more effective than using SASP alone in the treatment of UC .Shenqifuzheng injection may play important role in the treatment of UC by inhibiting the expression of CX3CR1 on colonic mucosa .

Research progression of Fractalkine/cx3cr1 and microglia in retina diseases / 中华实验眼科杂志

Fractalkine (Fkn) is the only member of CX3C subfamily of chemokine currently found,cx3cr1 is its specific receptor.Fkn/cx3cr1 is involved in inflammation,cancer,autoimmune diseases,allergy,acquired immune deficiency syndrome and other diseases,while its variety of pathophysiological role is accomplished by microglia.Functions of Fkn/cx3cr1 and microglia in age-related macular degeneration,acute light damage disease,retinal vascular disease,diabetic retinopathy disease,uveitis and other retina disease were reviewed in this article.

Expression and significance of chemokine receptor CX3CR1 in rats with severe acute pancreatitis / 西安交通大学学报(医学版)

ABSTRACT:Objective To explore the expression of chemokine receptor CX3CR1 in severe acute pancreatitis (SAP)rats model and to estimate whether it can be a potential predictor of SAP.Methods Forty Sprague-Dawley rats were randomly divided into sham-operation (SO)group (n =20)and SAP group (n =20).Rats were killed at 6 h,12 h,24 h and 48 h after model induction.The serum level of CX3CR1 was measured by enzyme-linked immunosorbent assay (ELISA).The expression of CX3CR1 protein in the pancreas,lung and kidney were detected by immunohistochemistry.Results The serum level of CX3CR1 in SAP rats increased gradually after model induction and reached the peak at 24 h (542.4 pg/mL),which were significantly higher than those in SO group (P <0.05).The expression of CX3CR1 was found in the pancreas,lung and kidney tissues of SAP rats and higher than that in SO group.Meanwhile,the expression of CX3CR1 reached the peak at 24 h in the pancreas and lung and at 48 h in the kidney.Conclusion This study suggests that the chemokine receptor CX3CR1 may be one effective index for predicting the severity of acute pancreatitis and deserves further research.

Sickle Cell Trait (HbAS) is Associated with Increased Expression of Erythrocyte Complement Regulatory Proteins CR1 and CD55 Levels in Children.

Aims: Erythrocyte complement regulatory proteins, complement receptor 1 (CR1) and decay accelerating factor (CD55) protect red blood cells (RBCs) from complement mediated damage by controlling complement activation cascade and potentially protect RBCs from complement mediated damage that may occur when immune complexes are formed following malaria infection. Given the important role of RBCs in regulation of complement activation, we considered the competence of sickle cell trait RBCs in these functions. Methods: Children (age 0-192 months; n=116) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu west District between October and December 2004. Based on hemoglobin (Hb) type, children were stratified into those with HbAS (n=47) and HbAA (n=69). The 47 HbAS individuals were matched to the 69 HbAA individuals of similar age (± 2 months or ± 24 months for those below or more than 192 months, respectively) at a ratio of 1:1 or 1:2. Circulating CR1 levels and CD levels were quantified using a FACScan cytometer under normal and reduced oxygen saturation. Results: The mean CR1 copy numbers per RBC was comparable in the two groups. However, between the ages of 49-192 months, the mean CR1 copy numbers per erythrocyte was significantly higher in children who had HbAS compared to those with HbAA (P=0.0332). The mean CD55 levels were comparable between the two groups but after deoxygenation, the mean CD levels in RBCs of individuals with HbAS was significantly higher than in the HbAA (P=0.011). Conclusion: The mean CR1 and CD55 copy numbers per RBC were comparable between the two groups under normal and reduced oxygen saturation. Beyond the age of 49 months, the CR1 copy numbers was higher in the HbAS compared to HbAA and this was also true for CD55 levels under deoxygenated conditions. Taken together, these results demonstrate that in the younger age groups, the protection afforded by HbAS against severe manifestations of malaria may be due to other factors other than complement regulatory proteins but beyond the age of 49 months, this protection may be partly due to the high CR1 copy numbers in the HbAS individuals.

Anaemia & expression levels of CD35, CD55 & CD59 on red blood cells in Plasmodium falciparum malaria patients from India.

Background & objectives: Severe anaemia in Plasmodium falciparum (Pf) associated malaria is a leading cause of death despite low levels of parasitaemia. In an effort to understand the pathogenesis of anaemia we studied expression level of RBC complement regulatory proteins, CR1 (CD35), CD55 and CD59 with haemoglobin status in a group of malaria cases from Assam, Goa and Chennai, and in healthy controls. Methods: Flowcytometry was used to study expression of CR1, CD55 and CD59 in 50 Pf cases and 30 normal healthy volunteers. Giemsa stained thick and thin blood films were used for microscopic detection and identification of malarial parasites and parasite count. Results: No correlation was found between degree of expression of RBC surface receptors CR1, CD55 and CD59 with haemoglobin level. However, expression of CD55 was less in malaria cases than in healthy controls. Interpretation & conclusions: The present findings indicate that malaria infection changes the expression profile of complement regulatory protein CD55 irrespective of severity status of anaemia. Further studies are needed to explore the pathophysiology of anaemia in malaria cases in Assam where expression of RBC complement receptors appears to be low even in normal healthy population.

Sequential Changes of CX3CR1 in Dorsal Root Ganglion in a Rat Model of Lumbar Disc Herniation

OBJECTIVE: To investigate the pain-related behaviors and the changes of CX3CR1 expression in the dorsal root ganglion (DRG) in a rat model of lumbar disc herniation. METHOD: A total of 90 male Sprague-Dawley rats were used. A laminectomy was performed to expose left L5 nerve roots and corresponding DRG. Autologous nucleus puplosus was implanted on the left L5 nerve root proximal to the DRG without mechanical compression. Sham operation was also done with the same procedure as mentioned above. Thermal hyperalgesia and mechanical allodynia were assessed at 1, 5, 10, 20 and 30 days after surgery. Real time PCR and immunohistochemistry after behavioral test were performed. RESULTS: In the lumbar disc herniation rats, significant reduction of thermal withdrawal latency indicating thermal hyperalgesia was shown on the ipsilateral hindpaw on postoperative day 1 (p<0.01) and peaked on day 10 (p<0.05) and maintained throughout day 30 (p<0.05). The reduction of mechanical allodynia threshold, indicating mechanical allodynia, was observed on the ipsilateral hindpaw on postoperative day 1 (p<0.01) and continued throughout day 30 (p<0.01). Real time PCR showed the decrease in mRNA expression of CX3CR1 in the ipsilateral DRG on day 1 (p<0.05) and the significant increase on day 20 (p<0.05). The immunoreactivity for CX3CR1 was also increased in ipsilateral DRG on day 10 and 20. CONCLUSION: These data suggest that lumbar disc herniation induces thermal hyperalgesia and mechanical allodynia and upregulates the expression of CX3CR1 in dorsal root ganglion. Expression of CX3CR1 might be associated with subacute neuropathic pain after intervertebral disc herniation.

Association between Knops blood group polymorphisms and susceptibility to malaria in an endemic area of the Brazilian Amazon

Complement receptor 1 (CR1) gene polymorphisms that are associated with Knops blood group antigens may influence the binding of Plasmodium parasites to erythrocytes, thereby affecting susceptibility to malaria. The aim of this study was to evaluate the genotype and allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) of Knops blood group antigens and examine their association with susceptibility to malaria in an endemic area of Brazil. One hundred and twenty-six individuals from the Brazilian Amazon were studied. The CR1-genomic fragment was amplified by PCR and six SNPs and haplotypes were identified after DNA sequence analysis. Allele and haplotype frequencies revealed that the Kn b allele and H8 haplotype were possibly associated with susceptibility to Plasmodium falciparum. The odds ratios were reasonably high, suggesting a potentially important association between two Knops blood antigens (Kn b and KAM+) that confer susceptibility to P. falciparum in individuals from the Brazilian Amazon.

Role of CR1 Knops polymorphism in the pathophysiology of malaria: Indian scenario.

Background & objectives: Plasmodium falciparum is the leading cause of mortality and causes cerebral malaria associated with sequestration caused by cytoadherence of the trophozoite and schizont-infected erythrocytes to the endothelial cells of the deep vascular beds in the brain. Pathophysiology of malaria is complicated by rosetting. Rosetting is a process of binding of uninfected erythrocytes to the erythrocytes infected with mature asexual parasites and is controlled by expression of complement receptor 1 (CR1) on RBC surface. Various polymorphic forms of CR1 are known including molecular weight polymorphism, red blood cell expression levels/density polymorphism and Knops (KN) polymorphism. The Knops blood group includes several allelic pairs; Knops a and b (Kna and Knb), McCoy a and b (McCa, McCb), Swain-Langley (Sla), and Villien (Vil). Knops phenotype Sl (a–) has been found to rosette less effectively than Sl (a+) and hence suggested to be more protective. P. falciparum cases have not reduced much as compared to the reduction in the total number of malaria cases in the past few years. In addition, P. falciparum is the leading cause for all mortality and most of the morbidity in India. We, therefore, investigated the role of CR1 Knops polymorphism in the pathophysiology of malaria in Indian population. Methods: A case control approach was used for this study. CAPS (Cleaved amplified polymorphic sequence) methodology was adopted. A total of 100 normal individuals (free from any ailment) and 100 individuals suffering from P. falciparum infection (uncomplicated malaria) were recruited for this study. Results: We found that in Indian population (normal individuals and P. falciparum-infected individuals), only the wild type allele is present. Interpretation & conclusion: We concluded that the process of rosetting in the Indian context could be occurring independently of the effect of Knops polymorphism and in part could be controlled by other polymorphisms of the CR1 gene (density and structural polymorphism).

Relationship between polymorphisms of CX3CR1 gene and coronary artery disease: a Meta-analysis / 基础医学与临床

Objective To find whether CX3CR1 V249I and T280M are associated with CAD. Methods Database in English and Chinese, including PUBMED, EMbase, were searched to get the case-control studies on the associa-tion between V249I, T280M and CAD. Results Six studies were reviewed. The pooled OR of V249I compared to wild type allele was OR =0. 85(95% CI =0. 67 ～ 1. 08,P >0. 05). The pooled OR of T280M compared to wild type allele was OR =0. 82(95% CI =0. 70 ～ 0. 96, P < 0. 05). Conclusion The T280M is a protective factor of CAD, while the V249I is not associated with CAD.

Study on chemokine receptor CX3CR1 gene T280M polymorphism in patients with ischemic cerebrovascular disease / 临床神经病学杂志

Objective To investigate chemokine receptor CX3CR1 gene T280M polymorphism in patients with ischemic cerebrovascular disease(ICVD) and its frequency.Methods 165 patients with ICVD(cerebral infarction 85 cases,lacunar infarction 40 cases,transient ischemic attack 40 cases) and 150 age- and sex-matched healthy controls(normal control group) were involved in this study.The polymorphism of T280M was analyzed by multiplex polymerase chain reaction-restriction fragment length based(PCR-RFLB),the gene frequency was compared between two groups and each ICVD subgroups.Results There were TT and TM genotypes in normal control group,and TT,TM and MM genotypes in ICVD group.The genotype were significant differences between the two groups(P0.05).Conclusions There is MM genotype in the chemokine receptor CX3CR1 gene T280M in the patients with ICVD,and their M allele frequency obviously increase.It suggests that CX3CR1 gene T280M polymorphism may be associated with ICVD.

Effects of glucocorticoids on the expression of fractalkine and CX3CR1 in kidneys of BXSB mice / 中国病理生理杂志

AIM:To observe the expression of chemokine fractalkine,and its receptor,CX3CR1,in kidneys of lupus-prone BXSB mice,and their changes after treatment with prednisone. The role of fractalkine and CX3CR1 in the pathogenesis of lupus nephritis was also discussed. METHODS:Twelve 12-week-old male BXSB mice were randomly divided into two groups,the prednisone treatment group (BXSB-prednisone group,n=6) and the experimental control group (BXSB group,n=6). Six male C57BL/6J mice at the same weeks of age served as a normal control group (C57BL/6J group). Both the C57BL/6J and the BXSB group of mice received a daily intragastric administration of 0.5 mL normal saline. The BXSB-prednisone group of mice was given a daily intragastric administration of prednisone (0.18 mg/20 g BW) dissolved in 0.5 mL normal saline. All treatments lasted for 10 weeks. The mRNA and protein expressions of fractalkine and CX3CR1 in kidneys of mice were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis respectively. The changes of laboratory index and the kidney histopathology of mice were also investigated. RESULTS:The mRNA and protein expressions of fractalkine and CX3CR1 in kidneys of BXSB mice were significantly higher than those in C57BL/6J mice. The expressions of fractalkine and CX3CR1 in BXSB-prednisone group of mice were much lower than those in BXSB group of mice,accompanied by the lower serum IgG,IgM and anti-dsDNA antibody levels as well as blood urea nitrogen,serum creatinine and urine protein. The glomerular immune complex deposition and the kidney histopathology were also significantly improved in BXSB-prednisone group of mice. CONCLUSION:These results indicate that fractalkine and CX3CR1 participate in the pathogenesis of lupus nephritis in BXSB mice,and the effect of glucocorticoids treatment may be attributed,in part,to its ability to inhibit the expression of fractalkine in kidney.