Activation of human monocytes-macrophages by OHR-AVR118 promotes both pro- and Anti-Inflammatory phenotypesReportar como inadecuado




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The immunomodulator OHR-AVR118 has been shown to increase IL-8 and MCP-1 secretion from non-activated human monocytes andU937 pro-monocytic cells, but to decrease MCP-1 secretion from LPS-activatedmonocytes, suggesting its effect depends on immune cell environment and-oractivation state. We therefore assessed the effect of OHR-AVR118 on cytokine secretion by human PBMCs and adherent monocytes. OHR-AVR118 increasedIL-6, IL-1β, and TNF-α secretion byPHA-IL-2-primedPBMCs, but did not alter IL-12 secretion. In contrast, treatment of LPS-activatedmonocytes decreased TNF-α and IL-12,increased IL-6, but did not alter IL-1β,secretion. To further show that the effect of OHR-AVR118 depends on cellular environment, we monitored U937differentiation towards mature macrophages in the presence of drug. OHR-AVR118 promoted a pro-inflammatoryresponse in PMA-activated cells, as demonstrated by increased expression of thematuration markers CD86, CD32, and CD87 and by increased IL-8, MCP-1, and GM-CSFsecretion. In undifferentiated U937 cells, OHR-AVR118 did not alter phagocytosis of opsonized S. aureus and IL-10 secretion. Whereas,after activation, OHR-AVR118induced an anti-inflammatory phenotype, as indicated by reduced phagocytosisand increased IL-10 secretion. Overall, these findings suggest that OHR-AVR118 has a dual action onmonocyte-macrophage function depending on cellular activation state,resulting in either further activation or suppression.

KEYWORDS

Peptide-Nucleic Acid; Monocytes; Chemokines; Cytokines; Inflammation

Cite this paper

Hirchman, S. 2014 Activation of human monocytes-macrophages by OHR-AVR118 promotes both pro- and Anti-Inflammatory phenotypes. Advances in Bioscience and Biotechnology, 5, 161-168. doi: 10.4236-abb.2014.53020.





Autor: Shalom Z. Hirchman

Fuente: http://www.scirp.org/



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