Disease relevance of Ccl2

• Using the F344-to-LEW rat model, intragraft gene transfer of chemokine analogs prolonged cardiac allograft survival from 10.1+/-0.7 and 10.4+/-0.7 days using non-coding adenovirus and vehicle alone, respectively, to 17.0+/-0.7 days for 8ND-RANTES (P<0.001) and 14.2+/-0.8 days for 8ND-MCP-1 (P<0.01) [1].
• Monocyte chemoattractant protein-1 mediates monocyte/macrophage influx in anti-thymocyte antibody-induced glomerulonephritis [2].
• RESULTS: Time-dependent elevation of MCP-1 expression was dramatically suppressed by treatment with the angiotensin-converting enzyme inhibitor enalapril or the AT1 receptor antagonist candesartan, and was closely associated with effects on proteinuria and glomerular macrophage number [3].
• Monocyte/macrophage infiltration to the subendothelial space of arterial wall is a critical initial step in atherogenesis, in which CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) is thought to play a key role [4].
• Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis factor-alpha [5].

Psychiatry related information on Ccl2

• After intracerebroventricular injections of MCP-1/CCL2, we showed that motor activity was markedly decreased [6].

High impact information on Ccl2

• In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by >50% after rhEPO administration [7].
• Repeated administration of the constructs encoding MCP-1, MIP-1 alpha, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease [8].
• Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that stimulates monocyte recruitment when injected into tissues of healthy animals [9].
• Chronic inflammation upregulates chemokine receptors and induces neutrophil migration to monocyte chemoattractant protein-1 [9].
• MCP-1 elicited increased leukocyte transendothelial migration in adjuvant-immunized rats compared with naive animals [9].

Chemical compound and disease context of Ccl2

• A single infusion of anti-TNF-alpha antibody at the time of glucan infusion (time 0) markedly reduced MCP-1 mRNA levels at 1 and 6 hours but not at later time points; there was no effect on granuloma size or number measured at 48 hours [10].
• Severe hypoxia (3% O2) potentiated the growth-promoting effect of MCP-1, which was able to significantly induce cell proliferation even at a concentration as low as 0.1 pg/ml [11].
• Ang II may thus promote atherogenesis by direct activation of MCP-1 gene expression in vascular smooth muscle cells [12].
• Our results indicate that glucose induces MCP-1 mainly through hyperosmolarity by activating PKC and its downstream NF-kappaB, and that such effect was inhibited by prednisolone, suggesting the efficacy of prednisolone in preventing peritoneal fibrosis in patients on CAPD [13].
• We used a reproducible model of focal excitotoxic brain injury elicited by intrahippocampal injection of NMDA (10 nmol) in 7-day-old rats, to examine injury-induced alterations in MCP-1 and CCR2 expression [14].

Biological context of Ccl2

• We conclude that chronic rejection of kidney allografts in rats is predominantly a local macrophage-dependent event with intense up-regulation of macrophage products such as MCP-1, IL-6, and inducible nitric oxide synthase [15].
• These data demonstrate that TGF-beta 1 functions as an inhibitor of MCP-1 expression in macrophages possibly via down-regulation of c-Jun/activator protein-1 [16].
• The antibody also significantly inhibited the gene expression of MCP-1, P-selectin, and intercellular adhesion molecule-1 [17].
• By contrast, no sustained suppression of the cell adhesion molecules intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 or the classic MCP-1 stimulators tumor necrosis factor-alpha or interleukin-1beta followed RAS inhibition, and suppression of transforming growth factor-beta1 expression was transient [3].
• C-C chemokines [monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha] and C-X-C chemokines [MIP-2 and cytokine-induced neutrophil chemoattractant (CINC)-2alpha] mediate chemotaxis of monocytes and neutrophils, respectively [5].

Anatomical context of Ccl2

• MCP-1 was maximally expressed at 52 weeks, commensurate with a progressive increase in infiltrating macrophages [15].
• The level of ICAM-1 mRNA transcripts in the WK-5 rat endothelial cell line were markedly enhanced by MCP-1 [18].
• These results suggest that MCP-1 released by Kupffer cells early after ischemia-reperfusion modulates neutrophil-dependent tissue injury via ICAM-1 [18].
• We investigated the effects of monocyte chemoattractant protein-1 (MCP-1) produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion in rat liver by occluding the portal vein for 30 minutes [18].
• Treatment of J774.2 macrophages with conditioned medium from mesangial cells blunted the induction of MCP-1 by LPS [16].

Associations of Ccl2 with chemical compounds

• Macrophage infiltration occurred in parallel with the expression of VCAM-1 and MCP-1, and these inflammatory cells were present on the luminal surface of injured vessels during intimal lesion formation [19].
• However, simultaneous blockade of the ERK1/2 and ROS pathways by using PD098059 combined with diphenylene iodonium or N-acetylcysteine potently enhanced the ability of MAPK kinase inhibitors to abrogate MCP-1 mRNA expression (100+/-2% inhibition) [20].
• CONCLUSION: These data suggest that glomerular macrophage recruitment in experimental diabetes is largely determined by angiotensin-stimulated MCP-1 expression [3].
• Expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 adhesion molecules involved in SMCs migration was enhanced by AA, whereas EPA and DHA had no similar effects [21].
• Pretreatment of VSMCs with p38 MAPK inhibitors, SB203580 and SB202190, resulted in a dose-dependent inhibition of chylomicron remnants-induced MCP-1 mRNA and protein expression, whereas a MAPK kinase inhibitor, PD98059, had no effect on these responses [22].

Physical interactions of Ccl2

• In this study, using quantitative autoradiography, we studied the pharmacological properties of [125l]MCP-1/CCL2 binding in rat brain and we clearly showed the distribution of CCR2 receptors in cerebral cortex, nucleus accumbens, striatum, amygdala, thalamus, hypothalamus, hippocampus, substantia nigra, mammillary bodies and raphe nuclei [6].
• However, treatment with AT1-receptor antagonists did not influence binding of ATS to mesangial cells and subsequent complement activation indicating that the attenuated MCP-1 expression is not due to differences in delivery and binding of ATS to mesangial cells [23].

Regulatory relationships of Ccl2

• Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia-reperfusion of the liver in rats [18].
• An anti-TGF-beta 1 neutralizing Ab abolished the inhibitory effect exerted by the mesangial cell medium, and externally added TGF-beta 1 suppressed the MCP-1 expression by macrophages at both mRNA and protein levels [16].
• Together, PDGF and IL-1 beta synergistically induced MCP-1 expression [24].
• In the hippocampus, IL6 is most expressed at the adult stage and MCP1 exhibits an equal level of expression from day two to the adult stage [25].
• However, MCP-1 inhibition persisted until 24 h. rmIL-1beta-induced MIP-2 and tumor necrosis factor-alpha mRNA expression were decreased by 36 and 24%, respectively, after halothane exposure [26].

Other interactions of Ccl2

• Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload [27].
• Treatment of rats with anti-rat MCP-1 or anti-rat RANTES had no effect on the development of lung injury [28].
• Identification of an inhibitor targeting macrophage production of monocyte chemoattractant protein-1 as TGF-beta 1 [16].
• Expression of the NF-kappa B-regulated genes, vascular cell adhesion molecule (VCAM)-1 and monocyte chemotactic protein (MCP)-1, was apparent in SMCs within 4 hours after injury [19].
• Conversely, exogenously MIP-1 beta, but not RANTES or MCP-1, caused enhancement of the lung vascular leak [28].

Analytical, diagnostic and therapeutic context of Ccl2

• Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1 [15].
• Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, interleukin (IL)-6, and C-C chemokine ligand (CCL) 2/monocyte chemotactic protein (MCP)-1 were examined by RT-PCR and ELISA [29].
• When studied by Northern blotting, glomerular mRNA levels of MCP-1, and interleukin 1 beta (IL-1 beta) increased at three hours and 24 hours following the induction of the injury [2].
• IL-6, MCP-1, and MIP-2 protein levels were elevated in bronchoalveolar lavage fluid [30].
• Pathological changes of the knee joints and the source of monocyte chemoattractant factor-1 (MCP-1) secretion were also determined by histology and immunohistochemistry [31].

References