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.
Rats ; Animals ; Depression/drug therapy* ; Brain-Derived Neurotrophic Factor ; Neuroprotective Agents ; Tumor Necrosis Factor-alpha/metabolism* ; Neuroinflammatory Diseases ; Diabetes Mellitus ; Receptors, Glutamate ; CX3C Chemokine Receptor 1/genetics*

OBJECTIVETo investigate the expressions of chemokine receptors and interleukin (IL) receptors on the peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients and their correlations with clinical features as well as SLE disease activity index (SLEDAI).

METHODSThe mRNA expressions of chemokine receptors and IL receptors on PBMCs of 93 SLE patients and 30 healthy controls were detected by reverse transcription-polymerase chain reaction, including CCR2, CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCRS, CX3CR1, XCR1, IL-4R, and IL-10R. The clinical features of SLE patients were recorded. The correlations of chemokine receptors and IL receptors mRNA expressions with clinical features as well as SLEDAI were assayed using linear regression analysis.

RESULTSThe level of CCR5 mRNA in SLE patients (including active and inactive SLE) was significantly higher than that in healthy controls (P < 0.05), and there was no significant difference between active and inactive patients in this respect (P > 0.05). CX3CR1 mRNA expression significantly increased from healthy control to inactive SLE to active SLE in sequence. The others (except for CCR8, CXCR3, and IL-10R) in active SLE patients were significantly higher than those in both inactive SLE patients and healthy controls (all P < 0.05). There were positive correlations between SLEDAI and CCR2 (r = 0.424, t = 4.313, P < 0.001), CCR3 (r = 0.518, t = 5.410, P < 0.001), CCR4 (r = 0.376, t = 3.851, P < 0.001), CCR6 (r = 0.457, t = 4.513, P < 0.001), CXCR5 (r = 0.455, t = 4.629, P < 0.001), CX3CR1 (r = 0.445, t = 4.523, P < 0.001), as well as XCR1 (r = 0.540, t = 5.445, P < 0.001). And CCR5 mRNA expression level was positively correlated with IL-4R mRNA (r = 0.313, t = 2.353, P < 0.05). The patients with myositis and cutaneous vasculitis simultaneously showed lower levels of CCR5 and CX3CR1, and CCR5 expression was negatively correlated with the scores of SLEDAI in SLE cases accompanied by photosensitivity (r = 0.426, t = -2.155, P < 0.05).

CONCLUSIONIncreased expressions of CCR5 and CX3CR1 on PBMCs may be indicators in clinical survey for SLE.

Adolescent ; Adult ; CX3C Chemokine Receptor 1 ; Child ; Female ; Humans ; Leukocytes, Mononuclear ; immunology ; Lupus Erythematosus, Systemic ; etiology ; immunology ; Male ; Middle Aged ; RNA, Messenger ; blood ; Receptors, CCR5 ; genetics ; Receptors, Chemokine ; genetics ; Receptors, Interleukin-10 ; genetics ; Receptors, Interleukin-4 ; genetics

OBJECTIVETo observe the effect of simvastatin on expression of CX3CR1 in the monocytes in patients with acute coronary syndrome and investigate the non-lipid mechanisms of statins against atherosclerosis.

METHODSThe expression of CX3CR1 in the monocytes was measured by quantitative real-time RT-PCR in 63 patients with acute coronary syndrome confirmed by coronary arteriography after treatment with simvastatin at 10(-7) approximately 10(-5) mol/L for 4, 8 and 12 h, respectively.

RESULTSCX3CR1 expression in the monocytes treated with different concentrations of simvastatin was significantly lower than that in the control cells (P<0.05), and the expression in the cells treated with the agent for different time lengths was also significantly lower than that in the control cells (P<0.01).

CONCLUSIONSimvastatin can reduce CX3CR1 expression in the monocytes of the patients with acute coronary syndrome in a concentration- and time-dependent manner, so as to reduce the inflammation and stabilize the vascular plaques.

Acute Coronary Syndrome ; blood ; drug therapy ; CX3C Chemokine Receptor 1 ; Female ; Gene Expression ; drug effects ; Humans ; Hypolipidemic Agents ; therapeutic use ; Male ; Monocytes ; drug effects ; metabolism ; Receptors, Chemokine ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Simvastatin ; therapeutic use

OBJECTIVETo investigate the expression of fractalkine (FKN) and its receptor CX3CR1 in cardiac allografts and the effect of Cyclosporin A (CsA).

METHODSThree groups of rats underwent heterotopic cardiac transplantation, 45 cases in each group and 5 cases in control group: SD to SD regarded as isograft group (group A), Wistar to SD divided into CsA untreated allograft group (group B) and CsA treated allograft group (group C), normal SD rats as control group. The FKN mRNA expression was detected by one-step RT-PCR method and the expression of FKN and CX3CR1 protein was detected by standard ABC immunohistochemical technique.

RESULTSThe expression of FKN mRNA and protein was weak in both isografts and normal heart specimens. The changes of FKN mRNA expression were correlated with the process of acute allograft rejection. The peak of FKN mRNA expression (0.8 +/- 0.26) appeared on the seventh day after transplantation, which could be down-regulated by CsA significantly (t = 2.390, P < 0.05). FKN protein was located in endothelia cells and its receptor CX3CR1 was located in infiltrating mononuclear cells in allografts.

CONCLUSIONSUpregulation of FKN and its receptor was significantly correlated with the trafficking of mononuclear cells which play an important role in acute allograft rejection. It may be one of the important mechanisms of CsA to intervene the acute rejection by inhibiting the activation of the FKN-CX3CR1 pathway.

Acute Disease ; Animals ; CX3C Chemokine Receptor 1 ; Chemokine CX3CL1 ; Chemokines, CX3C ; genetics ; metabolism ; Cyclosporine ; pharmacology ; Graft Rejection ; immunology ; pathology ; prevention & control ; Heart Transplantation ; immunology ; pathology ; Immunohistochemistry ; Male ; Membrane Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptors, Cytokine ; genetics ; metabolism ; Receptors, HIV ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Homologous

OBJECTIVETo investigate the V249I and T280M allelic polymorphisms of human immunodeficiency virus (HIV) coreceptor CX3CR1 in HIV-1 infected and uninfected population of Chinese indigenous Han and Uygur people and to probe the association between I249-M280 haplotype and HIV-1 susceptibility as well as AIDS progression.

METHODSGenomic DNA of 223 Uygur subjects and 316 Han subjects were purified from PBMC. I249 and M280 allelic frequencies were identified by polymerase chain reaction (PCR)/nest polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. All data were tested by chi(2) or u statistics analysis.

RESULTSAllelic frequencies of I249 and M280 were 16.1% and 13.3% in Uygur people, and 3.3% and 2.4% in Han people. No obvious difference existed between three groups of either ethnic group. However the allelic frequencies of HIV infected population were higher than those of general population, and those of general population higher than those of HIV-1 high-risk group. There was a strong linkage between I249 and M280 (P almost zero).

CONCLUSIONSI249 mutation was the sine qua non of M280 mutation, and most I249 alleles were accompanied by M280. The frequency of I249-M280 haplotype in Uygur population (13.3%) was adjacent to Caucasian people (15.8%), and that of I249-T280 haplotype (2.8%) was obviously lower than Caucasian people (12.5%); while both of them in Han people were much lower (0.9% and 2.4%). I249-M280 haplotype could accelerate AIDS progression according to Faure et al, while might be associated with HIV-1 susceptibility.

Alleles ; Asian Continental Ancestry Group ; genetics ; CX3C Chemokine Receptor 1 ; China ; epidemiology ; ethnology ; Chromosomes, Human, Pair 3 ; Ethnic Groups ; HIV Infections ; epidemiology ; genetics ; virology ; HIV-1 ; genetics ; Haplotypes ; Humans ; Membrane Proteins ; genetics ; metabolism ; Point Mutation ; Polymorphism, Restriction Fragment Length ; Receptors, Chemokine ; genetics ; metabolism ; Receptors, HIV ; deficiency ; genetics ; physiology ; Risk Factors

OBJECTIVE: To evaluate therapeutic eff ect of siRNA-HDAC5 on non-obese diabetic (NOD) mice by using small interference RNA (siRNA) technique to knock down the expression of HDAC5 in spleen CD4+ T cells. METHODS: NOD mice, 12-weeks old, were randomly divided into 3 groups and were given normal saline, siRNA-Control or siRNA-HDAC5 through caudal vein injection. The spleens and other samples were collected at the 18th, 24th or 30th week. The blood glucose was tested by blood glucose meter. The urinary albumin and serum levels of IL-1, IL-6, IL-18, and TNF-α were detected by ELISA. The mRNA levels of CD11a, CCR5, and CX3CR1 in spleen CD4+ T cells were measured by quantitative Real-time PCR. The HDAC5 protein level in spleen CD4+ T cell was detected by Western blot. RESULTS: Compared with the control group, the siRNA-HDAC5 group showed a significant decrease in blood glucose, urine albumin excretion rate, serum cytokine and the mRNA levels of CD11a, CCR5, and CX3CR1, consist with the decrease in protein level of HDAC5. CONCLUSION Inhibition of HDAC5 expression in NOD mice could effectively alleviate the onset and development of kidney damage caused by diabetes.
Animals ; CD11a Antigen ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CX3C Chemokine Receptor 1 ; Cytokines ; blood ; Diabetes Mellitus, Experimental ; genetics ; therapy ; Enzyme-Linked Immunosorbent Assay ; Histone Code ; Histone Deacetylases ; genetics ; Mice ; Mice, Inbred NOD ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; therapeutic use ; Random Allocation ; Real-Time Polymerase Chain Reaction ; Receptors, CCR5 ; metabolism ; Receptors, Chemokine ; metabolism ; Spleen ; cytology