OBJECTIVETo investigate the effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model.

METHODSThirty four male New Zealand white rabbits were randomized into four groups including normal control group (n = 6), placebo group (n = 8), atorvastatin group (1.5 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10) and montelukast group (1 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10). Rabbits except those in normal control group were fed a high cholesterol diet for 12 weeks. Serum lipids were measured at 0, 8 and 12 weeks after intervention. The intima/media ratio, percentages of macrophages or smooth muscle cells in intima and the expression of MCP-1 mRNA were examined.

RESULTSAtherosclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significantly reduced neointima (0.32 +/- 0.12 and 0.34 +/- 0.10 vs. 1.12 +/- 0.36, P < 0.05) and macrophage content [(9.8 +/- 4.6)% and (11.2 +/- 3.7)% vs. (34.6 +/- 8.8)%, P < 0.05], increased SMC content [(18.6 +/- 6.9)% and (19.2 +/- 8.6)% vs. (5.2 +/- 2.3)%, P < 0.05] and inhibited expression of MCP-1 mRNA (0.42 +/- 0.08 and 0.40 +/- 0.06 vs. 2.36 +/- 0.48, P < 0.01). Montelukast had similar anti-atherogenetic effects as atorvastatin but had no influence on plasma lipids.

CONCLUSIONSMontelukast could attenuate atherosclerosis in this hypercholesterolemic rabbit model which might be attributed to its anti-inflammatory effects.

Animals ; Atherosclerosis ; metabolism ; Chemokine CCL2 ; metabolism ; Hypercholesterolemia ; Macrophages ; metabolism ; Rabbits ; Tunica Intima

OBJECTIVE: To investigate the expression of monocyte chemotactic protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR-2) in coronary atherosclerosis plaques between sidden coronary death (SCD) and non-SCD. Methods The expression levels of MCP-1 and CCR-2 in SCD group, coronary atherosclerosis group (non-SCD), control group (normal coronary artery) were detected by immunohistochemistry. RESULTS: Positive rates of MCP-1 among the three groups were 78%, 47%, and 0%, respectively, with significant expressing differences between each two groups (P<0.05). Positive rates of CCR-2 among three groups were 72%, 47%, and 0%, respectively, with significant expressing differences between the SCD group and coronary atherosclerosis group as well as between the SCD group and control group (P<0.05), but with no significant expressing difference between coronary atherosclerosis group and control group (P>0.05). CONCLUSION Overexpression of MCP-1 and CCR-2 in coronary atherosclerotic plaques is closely correlated with SCD.
Chemokine CCL2/metabolism* ; Coronary Artery Disease/pathology* ; Death, Sudden, Cardiac/pathology* ; Humans ; Immunohistochemistry ; Receptors, CCR2/metabolism*

OBJECTIVETo explore lupus nephritis (LN) patients' monocyte chemotactic protein 1 (MCP-1) and urinary IP-10 (ulP-10) levels, the correlation between each clinical activity index and rheumatism syndrome, thereby proving objective evidence for microscopic typing of rheumatism syndrome.

METHODSTotally 60 LN patients were assigned to the rheumatism group (31 cases) and the non-rheumatism group (29 cases). Besides, 20 healthy volunteers were recruited as the normal control group. Clinical data and renal pathology were collected, and urinary levels of MCP-1 and IP-10 detected by ELISA. The correlation between rheumatism syndrome and each activity index as well as manifestations of clinical activities was comprehensively analyzed. Results (1) Patients in the rheumatism group were more liable to occur fever, serositis, edema, and hypertension (P<0.05). (2) Compared with the non-rheumatism group, patients in the rheumatism group exhibited much higher levels of 24 h protein quantification and blood urea nitrogen, higher levels of uMCP-1 and ulP-10. Microscopic hematuria, anti-ds-DNA, anti-Sm, the positive rate of AnuA, scores of SLEDAI and BILAG were higher in the rheumatism group than in the non-rheumatism group (P<0.05). Levels of plasma albumin and complement C3 were lower in the rheumatism group than in the non-rheumatism group (P<0.05). (3) The average activity index (AI) of the renal pathology was higher in the rheumatism group than in the non-rheumatism group. The most frequent pathological type of rheumatism group was type IV of LN.

CONCLUSIONSMore severe renal damage and immune abnormality occurred in LN patients of rheumatism syndrome. Rheumatism syndrome is closely correlated to clinical activity indices.

Biomedical Research ; Chemokine CCL2 ; metabolism ; Complement C3 ; metabolism ; Hematuria ; Humans ; Kidney ; Lupus Nephritis ; epidemiology ; metabolism ; Rheumatic Diseases ; epidemiology ; metabolism

OBJECTIVETo investigate the effects of cordyceps acid and cordycepin on the inflammatory phenotype and fibrogenic property of hepatic stellate cells (HSCs).

METHODSAn immortalized mouse HSC line (JS1) was stimulated with lippolysaccharide (LPS; 100 ng/ml) to induce an inflammatory response with or without co-administration of cordyceps acid or cordycepin in various concentrations (10, 50, or 200 mumol/L). Effects of the treatments on the chemokine monocyte chemotactic protein-1 (MCP-1) mRNA expression in the cells and the protein secretion in the cell culture supernatants were determined by reverse transcription and real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. In addition, JS1 cells were treated with transforming growth factor-b1 (TGFb1; 10 ng/ml) to induce a fibrogenic response with or without co-administration of cordyceps acid or cordycepin in various concentrations (10, 50, or 200 mumol/L). Effects on the expression of fibrogenic proteins including collagen type I and a-smooth muscle actin (a-SMA), were investigated by Western blot.

RESULTSHigh-concentration (200 mumol/L) treatments of both cordyceps acid and cordycepin significantly inhibited the LPS-induced up-regulation of MCP-1 transcription and secretion (mRNA: 2.07 +/- 0.29 vs. 3.35 +/- 0.26, t = 15.90 and 1.15 +/- 0.23 vs. 4.17 +/- 0.61, t = 8.93; protein: 1.88 +/- 0.06 vs. 2.33 +/- 0.06, t = 10.39 and 1.47 +/- 0.25 vs. 1.97 +/- 0.04, t = 4.60; all P less than 0.05). All concentrations of cordyceps acid and cordycepin inhibited the TGFb1-induced up-regulation of collagen type I and a-SMA protein expression. However, the effects were more robust with the 200 mumol/L concentrations (P less than 0.05).

CONCLUSIONCordyceps acid and cordycepin ameliorate the LPS-induced inflammatory phenotype and TGFb1-induced fibrogenic response of cultured HSCs. These effects may contribute significantly to the drugs' therapeutic mechanisms to inhibit and resolve liver fibrosis.

Animals ; Cells, Cultured ; Chemokine CCL2 ; metabolism ; Cordyceps ; Hepatic Stellate Cells ; metabolism ; Transforming Growth Factor beta1 ; metabolism ; Up-Regulation ; drug effects

OBJECTIVETo investigate the mechanism of monocyte chemoattractant protein-1 (MCP-1) regulations of human gingival fibroblasts (HGF) by challenge of Porphyromonas gingivalis (Pg) with different fimA genotypes.

METHODSPg ATCC 33277 (type I), WCSP115 (type II), WCSP1.5 (type III), W83 (type IV) were assessed for their inductions of MCP-1 expression in HGF. MCP-1 mRNA levels of HGF were determined by real-time RT-PCR and MCP-1 protein levels in culture supernatant by ELISA at different time intervals (1 h, 3h, 6h and 12h) following continuous co-culture of bacteria with HGF.

RESULTSMCP-1 mRNA and protein levels were both up-regulated when HGF co-cultured with different Pg fimA genotypes. Type II was stronger than other fimA genotypes, HGF expressed significantly great amount of MCP-1 mRNA [(25.75 +/- 3.12)-(326.69 +/- 35.35)] and protein [(178.20 +/- 46.20)-(443.46 82.19) ng/L] for different time periods; While Type III was weaker than other fimA genotypes, and the level of MCP-1 mRNA was [ (4.16 +/- 0.82)-(94.17 +/- 18.56)] and protein [(86.95 +/- 23.90)-(264.01 +/- 28.59) ng/L](P < 0.05).

CONCLUSIONSfimA genotypes of Pg are related with the inductions of MCP-1, which might indicate fimA genotype is associated with pathogenesis of Pg.

Cells, Cultured ; Chemokine CCL2 ; metabolism ; Fibroblasts ; metabolism ; Fimbriae Proteins ; genetics ; Genotype ; Gingiva ; cytology ; microbiology ; Humans ; Porphyromonas gingivalis ; genetics

OBJECTIVETo elucidate the roles of monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) on the vulnerability of atherosclerotic plaques in patients with stable (SAP) and unstable angina pectoris (UAP).

METHODSPatients with SAP (n = 50) and UAP (n = 50) underwent coronary angiography (CAG) and intravenous ultrasound (IVUS) were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immunosorbent assay (ELISA). mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR.

RESULTSIVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients (P < 0.05). SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients (P < 0.01). The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP (P < 0.01). Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients (P < 0.05 or P < 0.01). mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients (P < 0.05).

CONCLUSIONUpregulated monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) might promote coronary plaque vulnerability in UAP patients.

Angina Pectoris ; metabolism ; pathology ; Angina, Unstable ; metabolism ; pathology ; Chemokine CCL2 ; metabolism ; Chemokine CCL5 ; metabolism ; Chemokine CX3CL1 ; metabolism ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Plaque, Atherosclerotic ; pathology ; RNA, Messenger ; genetics

This study was aimed to explore the expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in bcr/abl fusion gene positive CML cells, and to study the effects of P210(bcr/abl) fusion protein tyrosine kinase on expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNAs in chronic myeloid leukemia cells. The expression levels of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNA were detected by semi-quantitative RT-PCR in bcr/abl negative cells, bcr/abl positive cells, and P210(bcr/abl)-Rb-C-Box positive cells. The results showed that MIP-1alpha and CCR-1 mRNAs were expressed in bcr/abl negative cells, but not in positive cells. Both MCP-1 and CCR-2 mRNA cannot be detected in both bcr/abl positive and negative cells. After inhibiting P210(bcr/abl) tyrosine kinase activity by Rb-C-Box, expressions of MIP-1alpha and CCR-1 mRNAs were restored to normal (similar to P210(bcr/abl) negative cells). It is concluded that P210(bcr/abl) fusion protein inhibits the expression of MIP-1alpha and CCR-1 in chronic myeloid leukemia cells, but does not inhibit MCP-1 and CCR-2 mRNA expressions in these leukemia cells.
Chemokine CCL2 ; biosynthesis ; genetics ; Chemokine CCL3 ; Chemokine CCL4 ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; Macrophage Inflammatory Proteins ; biosynthesis ; genetics ; Receptors, CCR1 ; Receptors, CCR2 ; Receptors, Chemokine ; biosynthesis ; genetics ; Tumor Cells, Cultured

Alcoholism ; metabolism ; Animals ; Brain ; metabolism ; Chemokine CCL2 ; genetics ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2 ; genetics ; metabolism

Objective To investigate the effects of miR-877-3p on migration and apoptotic T lymphocytes of bone mesenchymal stem cells (BMSCs). Methods The model of osteoporosis induced by bilateral ovariectomy (OVX) and sham operation was established. At 8 weeks after operation, the bone parameters of the two groups were detected by micro-CT. The levels of monocyte chemotactic protein 1(MCP-1) in BMSCs were detected by ELISA. BMSC in OVX group and sham group were co-cultured with T lymphocytes, respectively. The migration ability of T lymphocytes in the two groups was observed by Transwell^TM assay with PKH26 staining and apoptosis of T lymphocytes were detected by flow cytometry. Reverse transcription PCR was used to detect the expression of miR-877-3p in BMSCs. miR-877-3p was overexpressed or down-regulated by cell transfection. The level of MCP-1 secreted by BMSCs in each group was detected by ELISA. The migration and apoptosis of T lymphocytes were detected by the above methods. Results The number of trabecular bone and bone mineral density in OVX group were lower than those in sham group. The levels of MCP-1 secretion, chemotactic and apoptotic T lymphocyte ability of BMSCs in OVX group were also lower than those in sham group. The expression level of miR-877-3p in BMSC in OVX group was higher than that in sham group. After overexpression of BMSC miR-877-3p, the levels of MCP-1 secreted from BMSCs, and apoptotic T lymphocytes decreased, while the results were opposite after down-regulation of miR-877-3p. Conclusion miR-877-3p may be one of the causes of osteoporosis by inhibiting MCP-1 secretion of BMSCs and the migration and apoptosis of T lymphocytes.
Animals ; Female ; Mice ; Apoptosis/genetics* ; Bone Marrow Cells/metabolism* ; Cell Differentiation ; Chemokine CCL2/metabolism* ; Mesenchymal Stem Cells/metabolism* ; MicroRNAs/metabolism* ; Osteogenesis ; Osteoporosis/genetics* ; T-Lymphocytes/metabolism*

OBJECTIVETo explore the role of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in myocardial ischemia/reperfusion injury (MI/RI) by observing the dynamic expression changes at mRNA and protein levels early after myocardial ischemia/reperfusion (I/ R).

METHODSThe Wistar rats were randomly divided into Sham and I/R group (n = 42), and killed according to different reperfusion time (1, 2, 4, 6, 12, 24 h and 7 d). Structural and morphous changes of myocytes were observed under optical microscope. The mRNA and protein levels of TLR2 and TLR4 were detected using real-time PCR (RT-PCR). Monocyte chemokine protein-1 (MCP-1) and interleukine-6 (IL-6) mRNA levels were measured by reverse transcriptase-polymerase chain reaction (rt-PCR).

RESULTS(1) With the extension of reperfusion time, the myocardial infarct size increased smoothly, and reached the plateau at 4 h, then stayed in the platform. After reperfusion for 7 d, the ventricular had been remodeled. (2) At the beginning of reperfusion, myocardial structure showed no significant change in Sham group, but had different degrees of injury in I/R group. In rats of the group reperfused for 7 d the left ventricular remodeling could be visible. (3) Compared to sham group,TIR2, TLR4, MCP-1, IL-6 mRNA level were increased in myocardium in I/R group. TLR2 and TLR4 both peaked at 4 h of reperfusion, IL6 peaked at 6 h, followed by a gradually decrease. TLR4 and IL-6 mRNA levels rose again at 7 d. MCP-1 level in I/R group remained fairly with sham group at the beginning of reperfusion, and markedly elevated at 7 d.

CONCLUSIONExpression of TLRs mRNA in myocardium during early after myocardial ischemia/reperfusion increased rapidly and activated TLRs might play an important role in MI/RI through promoting the generation of inflammatory factors. At the late reperfusion, TLRs levels raise again and the expression of inflammatory factors increase once again, Those may probably affect the remodeling of ventricular, and injure myocardial structure and function.

Animals ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; Interleukin-6 ; metabolism ; Male ; Myocardial Reperfusion Injury ; metabolism ; Rats ; Rats, Wistar ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism