Activation of human monocytes/macrophages by OHR/AVR118 promotes both pro- and Anti-Inflammatory phenotypes

作     者：Shalom Z. Hirchman 

作者机构：OHR Pharmaceutical Inc. New York USA 

出 版 物：《Advances in Bioscience and Biotechnology》 (生命科学与技术进展（英文）)

年 卷 期：2014年第5卷第3期

页      面：161-168页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Peptide-Nucleic Acid Monocytes Chemokines Cytokines Inflammation 

摘      要：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.