An amebic anti-inflammatory peptide down-regulates ex vivo IL-1ß expression in patients with rheumatoid arthritis.

UNLABELLED: The monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide produced by Entamoeba histolytica in culture. This factor displays several anti-inflammatory properties (i.e., inhibition of locomotion and respiratory burst in monocytes, reduction of skin hypersensitivity and delay of mononuclear cells in human Rebuck skin windows) with inhibition of adhesion molecules, chemokines, and other genes including interleukin-1ß (IL-1ß). In animal models, it reduces carragenin-induced inflammation and delays the inflammatory process in murine collagen-induced arthritis (CIA). OBJECTIVES: To test, in vitro, the anti-inflammatory capacity of MLIF on a promonocytic human cell line (U-937) cells and peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: IL-1ß gene expression was evaluated in cell cultures either in the presence of MLIF, lipopolysaccharide (LPS), or both. Relative gene expression and immunoreactivity of IL-1ß were assayed in cells and supernatants, respectively. RESULTS: Amebic peptide was able to down-regulate LPS-induced expression of IL-1ß, in U-937 cells without a detectable effect upon the bioavailability of the cytokine. In similar culture conditions, MLIF was capable to down-regulate baseline and LPS-induced expression of IL-ß only in PBMC from patients with RA. Peptide effect on immunoreactivity of IL-1ß was not statistically significant. CONCLUSIONS: MLIF exerts, in primed cells, exquisite anti-inflammatory properties that deserve to be explored mechanistically.

An amebic anti-inflammatory peptide down-regulates ex vivo IL-1Beta expression in patients with rheumatoid arthritis

El factor inhibidor de la locomoción de monocitos (FILM) es un pentapéptido termoestable producido por Entamoeba histolytica en cultivo. Este factor presenta diversas propiedades antiinflamatorias, a saber: inhibición de la locomoción y estallido respiratorio en monocitos, abatimiento de la hipersensibilidad por contacto al dinitroclorobenceno y retraso de la quimitoaxis de células mononucleares, disminución en la expresión de moléculas de adhesión y quimiocinas entre otros genes. En ratones el FILM reduce la inflamación inducida por carragenina y retrasa el proceso inflamatorio de la artritis inducida por colágena. Objetivo: Evaluar in vitro el efecto del FILM sobre la expresión de IL-1Beta en la línea celular promonocítica humana (U-937) y en células mononucleares de sangre periférica provenientes de donadores sanos y de pacientes con artritis reumatoide. Material y Métodos: Se realizaron cultivos celulares en presencia de FILM, lipopolisacárido o ambos. Después del cultivo se determinó expresión relativa e inmunoreactividad de IL-1Beta en los botones celulares y sobrenadantes respectivamente. Resultados: El péptido amibiano pudo reducir la expresión de IL-1Beta inducida por LPS en células U937, sin mostrar un efecto detectable sobre la biodisponibilidad de la citocina. En condiciones de cultivo similares, el FILM fue capaz de disminuir la expresión de IL-1Beta, basal e inducida por LPS, sólo en células mononucleares provenientes de pacientes con artritis. Su efecto sobre la inmunoreactividad de la citocina no fue significativo estadísticamente. Conclusiones: El FILM ejerce en las células activadas propiedades antiinflamatorias exquisitas que merecen ser exploradas mecanísticamente (AU)

The monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide produced by Entamoeba histolytica in culture. This factor displays several anti-inflammatory properties (i.e., inhibition of locomotion and respiratory burst in monocytes, reduction of skin hypersensitivity and delay of mononuclear cells in human Rebuck skin windows) with inhibition of adhesion molecules, chemokines, and other genes including interleukin-1Beta (IL-1Beta). In animal models, it reduces carragenin-induced inflammation and delays the inflammatory process in murine collagen-induced arthritis (CIA). Objectives: To test, in vitro, the anti-inflammatory capacity of MLIF on a promonocytic human cell line (U-937) cells and peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients with rheumatoid arthritis (RA). Material and methods: IL-1Beta gene expression was evaluated in cell cultures either in the presence of MLIF, lipopolysaccharide (LPS), or both. Relative gene expression and immunoreactivity of IL-1Beta were assayed in cells and supernatants, respectively. Results: Amebic peptide was able to down-regulate LPS-induced expression of IL-1Beta, in U-937 cells without a detectable effect upon the bioavailability of the cytokine. In similar culture conditions, MLIF was capable to down-regulate baseline and LPS-induced expression of IL-Beta only in PBMC from patients with RA. Peptide effect on immunoreactivity of IL-1Beta was not statistically significant. Conclusions: MLIF exerts, in primed cells, exquisite anti-inflammatory properties that deserve to be explored mechanistically (AU)