Effect monocyte chemoattractant protein

Villiger PM, Terkeltaub R, Lotz M. Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage. Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid. J Clin Invest 1992 90(2) 488 196. 

Han KH, Han KO, Green SR, Quehenberger O. Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia. Differential effects of plasma lipoproteins on monocyte function. J Lipid Res 1999 40(6) 1053-1063. 

Recent evidence suggests that atherosclerosis is a chronic inflammatory process. The recruitment of mononuclear leukocytes and formation of intimal macrophage-rich lesions at specific sites of the arterial tree are key events in atherogenesis. Alterations of chemotactic and adhesive properties of the endothelium play an important role in this process [82]. Quercetin has been reported to inhibit the expression in glomerular cells of monocyte chemoattractant protein-1 (MCP-1) [83] a potent chemoattractant for circulating monocytes. Red wine reduced MCP-1 mRNA and protein expression in abdominal aorta of cholesterol fed rabbits after balloon injury and this effect was associated with a reduced neointimal hyperplasia [84]. The antioxidant-mediated inhibition of nuclear factor k B (NFkB) and the subsequent non selective reduction of cytokine transcription have been suggested to be responsible for these effects [83]. Additionally, quercetin downregulated both phorbol 12-myristate 13-acetate (PMA)- and tumour necrosis factor-a (TNFa)-induced intercellular adhesion molecule-1 (ICAM-1) expression in human endothelial cells [86]. 

Cilostazol has a number of additional indirect effects. Similar to dipyridamole, it enhances the actions of prostacyclin, although it has not been reported to directly increase prostacyclin release, Cilostazol also affects endothelial cells, specifically the release of cytokines, such as monocytic chemoattractant protein-1 (MCP-1), which appears to play an important role in the development and progression of atherosclerotic lesions (24). Cilostazol, like other PDE3 inhibitors, acts as a vasodilator. 

N. G. Gourmala, M. Buttini, S. Limonta, A. Sauter, H. W. G. M. Boddeke, Differential and Time-Dependent Expression of Monocyte Chemoattractant Protein-1 mRNA by Astrocytes and Macrophages in Rat Brain Effects of Ischemia and Peripheral Lipopolysaccharide Administration, Journal of Neuroimmunology, 74 (1997) 35-44. 

A straightforward approach to in vivo hypothesis testing is to generate a knockout mouse for the gene of interest, inoculate with prions and look at the effect on incubation time as compared to wild type controls. Experiments of this nature have been carried out for the anti-inflammatory cytokines interleukin-4 (114), 1110 and 1113 and the chemokine, monocyte chemoattractant protein-1 (Mcpl) [82, 83]. Following intracerebral inoculation with the RML strain of mouse adapted scrapie, no significant differences were seen for mice deficient in either 114,1113 or both. However, for mice... 

The other broad category of MSP actions on macrophages relates to mediator production. Endotoxin, or combinations of proinflammatory cytokines, causes expression of murine macrophage-inducible nitric oxide synthase, an effect that can be detected by Northern blots for the mRNA or by measurement of nitrate in the culture fluid. MSP prevents induction of NO-synthase by any of the above stimuli (Wang et al., 1994d). The inhibitory action of MSP is confined to this specific mediator. MSP did not inhibit endotoxin-induced expression of mRNA for monocyte chemoattractant protein-1. Furthermore, MSP caused secretion of IL-6 (but not IL-1 or TNFa) within 6 hr, and did not inhibit endotoxin-induced secretion of IL-1, IL-6, or TNFa (A. Skeel and E. J. Leonard, unpublished data). The in vitro modulation by MSP of endotoxin-induced NO production now has an in vivo counterpart. Concentrations of nitrate in serum of Stk / mice that received endotoxin intravenously were higher than in serum of comparably treated normal mice and at a critical endotoxin dose, only 20% of the Stk / mice survived, compared to 80% survival for normal mice (Correll et al., 1997). If MSP plays a role in the host response to endotoxemia, pro-MSP must be cleaved to biologically active MSP. Within 4 hr after i.v. administration of... 

FIGURE 4 Densitometric analysis of Northern blots showing the effects of nitric oxide (NO) on the expression of monocyte chemoattractant protein (MCP-1) mRNA. Cultured human umbilical vein endothelial cells were incubated for 12 hr with solvent (control), the NO synthase inhibitor N°-nitro-L-arginine (L-NAG), or the NO donor SIN-1. Data were obtained using five different cell preparations. P < 0.01. 

While functional studies indicate that astrocytes possess TNF-Rs, the specific characterization of TNF-R 1 and TNF-R2 on human astrocytes under constitutive and activated conditions has not been well studied to date. The number of surface TNF-R 1 and TNF-R2 on human astrocytes has not been determined quantitatively there may be a differential expression of the two receptor types on astrocytes, as there is on epithelial and myeloid cells. Agonistic TNF-R antibodies, such as anti-TNF-Rl, mimic the effects of TNF by inducing normal human astrocytes to synthesize cytokines, such as IL-6 and monocyte chemoattractant protein 1, and to undergo growth modulation (Barna et al., 1993, 1994). Since anti-TNF-Rl but not anti-TNF-Rl antibodies induce an effect on normal human astrocytes, and only TNF-Rl transcripts are strongly detected in untreated fetal and adult astrocytes, it has been suggested that TNF-Rl is the predominant constitutive receptor type on human astrocytes (Barna et al., 1993 Tada et al., 1994). 

In addition, Maeda et ah (2009) reported that fucoxanthin-rich wakame lipids (WLs) had antiobesity and antidiabetic effects on HFD-induced obesity in mice. The increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA in HF mice was normalized by ingestion of WL with a HFD. Moreover, the HF-WL diet may ameliorate alterations in lipid metabolism and insulin resistance induced by a HFD by promoting... 

Goser, S., Otd, R., Brodner, A., Dengler, T.J., Torzewski, J., Egashira, K., Rose, N.R., Katus, H.A., and Kaya, Z. (2005) Critical role for monocyte chemoattractant protein-1 and macrophage inflammatory protein-lalpha in induction of experimental autoimmime myocarditis and effective anti-monocyte chemoattractant protein-1 gene therapy. Circulation, 112 (22), 3400-3407. 

It is now clear, of course, that chemokines are responsible for nearly all of the leukocyte-specific chemoattractant activity present in these preparations. In the case of monocyte-specific chemoattraction, such as that associated with TDCF, most of the activity was caused by monocyte chemoattractant protein-1 (MCP-1), a CC chemokine (5,6). In vitro, MCP-1 attracts monocytes with an EC50 of 500 pM (7,8). MCP-1 also attracts CD45RO T lymphocytes and triggers histamine release from basophils, but has no effects on neutrophils (9-11). 

Loetscher, P., Dewald, B., Baggiolini, M., and Seitz, M. (1994) Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes. Effects of anti-rheumatic drugs. Cytokine 6,162-170. 

Inhibition by niacin of inflammatory and oxidative pathways may exert anti-atherosclerotic effects. In cultured human aortic endothelial cells, niacin increased cellular levels of nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and glutathione, regulators of redox reactions, and reduced production of reactive oxygen species. Niacin inhibited monocyte adhesion through the inhibition of tumour necrosis factor-alpha (TNF-a) induced expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) (Ganji et al. 2009). Persistent increases in plasma adiponectin, an adipokine with anti-inflammatory properties, were found after 6 months of niacin treatment in humans (Linke et al. 2009). 

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