An anti-inflammatory oligopeptide produced by Entamoeba histolytica down-regulates the expression of pro-inflammatory chemokines.
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-1alpha, MIP-1beta, 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-1alpha, MIP-1beta, 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.
Utrera-Barillas
Dolores
D
Unidad de Investigación Médica en Inmunología IMSS, Secretaria de Salud, México DF, México.
Velazquez
Juan R
JR
Enciso
Antonio
A
Cruz
Samira Muñoz
SM
Rico
Guadalupe
G
Curiel-Quesada
Everardo
E
Teran
Luis M
LM
Kretschmer
Roberto R
RR
D000818:Animals; D054402:Chemokine CCL1; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000276:immunology; D002630:Chemotactic Factors / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D004748:Entamoeba histolytica / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D019707:Receptors, Chemokine / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology; D020298:U937 Cells
C065971:CCL1 protein, human; D054402:Chemokine CCL1; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D009842:Oligopeptides; D019707:Receptors, Chemokine; C430647:monocyte locomotion inhibitory factor; D012313:RNA; D013755:Tetradecanoylphorbol Acetate