title: Anti-inflammatory actions of phosphatidylinositol.
abstract: Chronic inflammatory T-cell-mediated diseases such as inflammatory bowel disease (IBD) are often treated with immunosuppressants including corticosteroids. In addition to the intended T-cell suppression, these farmacons give rise to many side effects. Recently, immunosuppressive phospholipids have been proposed as less-toxic alternatives. We aimed to investigate the immunoregulatory capacities of the naturally occurring phospholipid phosphatidylinositol (PI). Systemic PI treatment dramatically reduced disease severity and intestinal inflammation in murine 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Moreover, PI treatment inhibited the inflammatory T-cell response in these mice, as T cells derived from colon-draining LN of PI-treated mice secreted less IL-17 and IFN-γ upon polyclonal restimulation when compared to those of saline-treated mice. Further characterization of the suppressive capacity of PI revealed that the phospholipid suppressed Th cell differentiation in vitro irrespective of their cytokine profile by inhibiting proliferation and IL-2 release. In particular, PI diminished IL-2 mRNA expression and inhibited ERK1-, ERK-2-, p38- and JNK-phosphorylation. Crucially, PI did not ablate Treg differentiation or the antigen-presenting capacity of DCs in vitro. These data validate PI as a pluripotent inhibitor that can be applied mucosally as well as systemically. Its compelling functions render PI a promising novel physiological immune suppressant.
authors.affiliation: Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: van Dieren
authors.forename: Ytje
authors.initials: Y
authors.lastname: Simons-Oosterhuis
authors.forename: H C Rolien
authors.initials: HC
authors.lastname: Raatgeep
authors.forename: Dicky J
authors.initials: DJ
authors.lastname: Lindenbergh-Kortleve
authors.forename: Margaretha E H
authors.initials: ME
authors.lastname: Lambers
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Gerry T
authors.initials: GT
authors.lastname: Snoek
authors.forename: Ron
authors.initials: R
authors.lastname: Potman
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017951:Antigen Presentation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010716:Phosphatidylinositols / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010716:Phosphatidylinositols