Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer.
The monocyte-macrophage (MPhi) lineage can undergo different pathways of activation. The classical priming by IFN-gamma, then triggering by LPS, conducts MPhi toward proinflammatory responses, whereas the alternative activation by IL-4, IL-10, IL-13, or glucocorticoids directs them toward an anti-inflammatory, immunosuppressive phenotype. Recently, we have shown that synthetic phosphorus-containing dendrimers activate human monocytes. Here, we analyzed the gene expression of monocytes activated by an acid azabisphosphonic-capped, phosphorus-containing dendrimer by comparison with untreated monocytes. We found that 78 genes were up-regulated, whereas 62 genes were down-regulated. Analysis of these genes directed the hypothesis of an alternative-like, anti-inflammatory activation of human monocytes. This was confirmed by quantitative RT-PCR and analysis of the surface expression of specific markers by flow cytometry. Functional experiments of inhibition of CD4(+) T-lymphocyte proliferation in MLR indicated that dendrimer-activated monocytes (da-monocytes) have an immune-suppressive phenotype similar to the one induced by IL-4. Moreover, da-monocytes preferentially enhanced amplification of CD4(+) T cells, producing IL-10, an immunosuppressive cytokine. Therefore, phosphorus-containing dendrimers appear as new nanobiotools promoting an anti-inflammatory and immunosuppressive activation of human monocytes and thus, prove to be good candidates for innovative, anti-inflammatory immunotherapies.
Fruchon
Séverine
S
CHU Purpan, BP 3028, 31024 Toulouse Cedex, France. remy.poupot@inserm.fr.
Poupot
Mary
M
Martinet
Ludovic
L
Turrin
Cédric-Olivier
CO
Majoral
Jean-Pierre
JP
Fournié
Jean-Jacques
JJ
Caminade
Anne-Marie
AM
Poupot
Rémy
R
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects*
D050091:Dendrimers; D016753:Interleukin-10