Monocyte Chemotaxis (monocyte + chemotaxis)

Distribution by Scientific Domains

Selected Abstracts

An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines

Dolores Utrera-Barillas
SUMMARY Axenically grown Entamoeba histolytica produces a pentapeptide (Met-Gln-Cys-Asn-Ser) with anti-inflammatory properties that, among others, inhibits the in vitro and in vivo locomotion of human monocytes, sparing polymorphonuclear leucocytes from this effect [hence the name originally given: Monocyte Locomotion Inhibitory Factor (MLIF)]. A synthetic construct of this peptide displays the same effects as the native material. We now added MLIF to resting and PMA-stimulated cells of a human monocyte cell line and measured the effect upon mRNA and protein expression of pro-inflammatory chemokines (RANTES, IP-10, MIP-1,, MIP-1,, MCP-1, IL-8, I-309 and lymphotactin) and the shared CC receptor repertoire. The constitutive expression of these chemokines and the CC receptors was unaffected, whereas induced expression of MIP-1,, MIP-1,, and I-309, and that of the CCR1 receptor , all involved in monocyte chemotaxis , was significantly inhibited by MLIF. This suggests that the inhibition of monocyte functions by MLIF may not only be exerted directly on these cells, but also , and perhaps foremost , through a conglomerate down-regulation of endogenous pro-inflammatory chemokines. [source]

Statins suppress interleukin-6-induced monocyte chemo-attractant protein-1 by inhibiting Janus kinase/signal transducers and activators of transcription pathways in human vascular endothelial cells

Michihisa Jougasaki
Background and purpose:, The mechanisms of anti-inflammatory actions of statins, 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, remain unclear. We investigated the effects of statins on interleukin (IL)-6-induced monocyte chemo-attractant protein (MCP)-1 expression and monocyte chemotaxis. Experimental approach:, Cultures of human aortic endothelial cells (HAECs) were stimulated with IL-6 in the absence and presence of statins. Gene expression and protein secretion of MCP-1, phosphorylation of Janus kinase (JAK) and the signal transducers and activators of transcription (STAT) pathway, and human monocyte migration were examined. Key results:, IL-6 plus its soluble receptor sIL-6R (IL-6/sIL-6R) promoted THP-1 monocyte migration, and increased gene expression and protein secretion of MCP-1, more than IL-6 alone or sIL-6R alone. Various statins inhibited IL-6/sIL-6R-promoted monocyte migration and MCP-1 expression in HAECs. Co-incubation of mevalonate and geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, reversed the inhibitory effects of statins on MCP-1 expression. Geranylgeranyl transferase inhibitor, but not farnesyl transferase inhibitor, suppressed IL-6/sIL-6R-stimulated MCP-1 expression. IL-6/sIL-6R rapidly phosphorylated JAK1, JAK2, TYK2, STAT1 and STAT3, which were inhibited by statins. Transfection of STAT3 small interfering RNA (siRNA), but not STAT1 siRNA, attenuated the ability of IL-6/sIL-6R to enhance THP-1 monocyte migration. In addition, statins blocked IL-6/sIL-6R-induced translocation of STAT3 to the nucleus. Conclusions and implications:, Statins suppressed IL-6/sIL-6R-induced monocyte chemotaxis and MCP-1 expression in HAECs by inhibiting JAK/STAT signalling cascades, explaining why statins have anti-inflammatory properties beyond cholesterol reduction. [source]

Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists

Elena Riboldi
The present study was aimed to investigate the effect of benzydamine, an anti-inflammatory drug devoid of activity on arachidonic acid metabolism, on monocyte chemotaxis and to define the possible biochemical correlates of activity. Benzydamine inhibited monocyte chemotaxis in response to three classes of chemoattractants: the prototypic CC-chemokine CCL2 (MCP-1), the microbial product fMLP and the complement cascade component C5a. The effect was dose-dependent with IC50's of 100, 50 and 45 ,M for MCP-1/CCL2, fMLP and C5a, respectively. At the dose of 100 ,M, the effect resulted in a 5010% inhibition of MCP-1/CCL2-induced chemotaxis and 536 and 545% inhibitions of chemotaxis in response of fMLP and C5a, respectively (n=3). Receptor expression as well as calcium fluxes in response to chemoattractants were not affected by benzydamine. Benzydamine strongly inhibited chemoattractant-induced activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and of its upstream activator kinase MEK1/2. ERK1/12 activation in response to chemoattractants was 89,98% inhibited by a 100 ,M concentration of benzydamine with an IC50 of 30 ,M. Under the same experimental conditions, pretreatment with 100 ,M benzydamine caused a 75,89% inhibition of p38 activation (IC50 25 ,M). These results indicate that the anti-inflammatory activity of benzydamine is exerted at multiple levels, including monocyte migration to chemotactic factors associated to a blockage of ERK and p38 MAPK pathways. British Journal of Pharmacology (2003) 140, 377,383. doi:10.1038/sj.bjp.0705428 [source]