Simplexide induces CD1d-dependent cytokine and chemokine production from human monocytes.
Monocytes are major effector cells of innate immunity and recognize several endogenous and exogenous molecules due to the expression of wide spectrum of receptors. Among them, the MHC class I-like molecule CD1d interacts with glycolipids and presents them to iNKT cells, mediating their activation. Simplexide belongs to a novel class of glycolipids isolated from marine sponges and is structurally distinct from other immunologically active glycolipids. In this study we have examined the effects of simplexide on cytokine and chemokine release from human monocytes. Simplexide induces a concentration- and time-dependent release of IL-6, CXCL8, TNF-α and IL-10 and increases the expression of IL6, CXCL8 and IL10 mRNA. Cytokine and chemokine release induced by simplexide from monocytes is dependent on CD1d since: i) a CD1d antagonist, 1,2-bis (diphenylphosphino) ethane [DPPE]-polyethylene glycolmonomethylether [PEG], specifically blocks simplexide-induced activation of monocytes; ii) CD1d knockdown inhibits monocyte activation by simplexide and iii) simplexide induces cytokine production from CD1d-transfected but not parental C1R cell line. Finally, we have shown that simplexide also induces iNKT cell expansion in vitro. Our results demonstrate that simplexide, apart from activating iNKT cells, induces the production of cytokines and chemokines from human monocytes by direct interaction with CD1d.
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Stefania
S
Loffredo
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Rosaria I
RI
Staiano
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Francescopaolo
F
Granata
The NeaNAT group - Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Valeria
V
Costantino
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Francesco
F
Borriello
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Annunziata
A
Frattini
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Maria Teresa
MT
Lepore
The NeaNAT group - Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Alfonso
A
Mangoni
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Gianni
G
Marone
Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
Massimo
M
Triggiani
D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006017:Glycolipids / Q000737:chemistry*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology; D011161:Porifera; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D055610:Antigens, CD1d; C508606:CXCL8 protein, human; D018925:Chemokines; D016207:Cytokines; D006017:Glycolipids; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; C000599346:simplexide; D016753:Interleukin-10