TITLE:
Activation of human monocytes/macrophages by OHR/AVR118 promotes both pro- and Anti-Inflammatory phenotypes
AUTHORS:
Shalom Z. Hirchman
KEYWORDS:
Peptide-Nucleic Acid; Monocytes; Chemokines; Cytokines; Inflammation
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.5 No.3,
January
29,
2014
ABSTRACT:
The immunomodulator OHR/AVR118 has been shown to increase IL-8 and MCP-1 secretion from non-activated human monocytes and
U937 pro-monocytic cells, but to decrease MCP-1 secretion from LPS-activated
monocytes, suggesting its effect depends on immune cell environment and/or
activation state. We therefore assessed the effect of OHR/AVR118 on cytokine secretion by human PBMCs and adherent monocytes. OHR/AVR118 increased
IL-6, IL-1β, and TNF-α secretion byPHA/IL-2-primed
PBMCs, but did not alter IL-12 secretion. In contrast, treatment of LPS-activated
monocytes 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 U937
differentiation towards mature macrophages in the presence of drug. OHR/AVR118 promoted a pro-inflammatory
response in PMA-activated cells, as demonstrated by increased expression of the
maturation markers CD86, CD32, and CD87 and by increased IL-8, MCP-1, and GM-CSF
secretion. In undifferentiated U937 cells, OHR/AVR118 did not alter phagocytosis of opsonized S. aureus and IL-10 secretion. Whereas,
after activation, OHR/AVR118
induced an anti-inflammatory phenotype, as indicated by reduced phagocytosis
and increased IL-10 secretion. Overall, these findings suggest that OHR/AVR118 has a dual action on
monocyte/macrophage function depending on cellular activation state,
resulting in either further activation or suppression.