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Anti-inflammatory actions of phosphatidylinositol

Authors
  • van Dieren, Jolanda M
  • Simons-Oosterhuis, Ytje
  • Raatgeep, HC (Rolien)
  • Lindenbergh-Kortleve, Dicky J
  • Lambers, Margaretha EH
  • van der Woude, C Janneke
  • Kuipers, Ernst J
  • Snoek, Gerry T
  • Potman, Ron
  • Hammad, Hamida
  • Lambrecht, Bart
  • Samsom, Janneke N
  • Nieuwenhuis, Edward ES
Publication Date
Jan 01, 2011
Source
Ghent University Institutional Archive
Keywords
Language
English
License
Unknown
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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-gamma 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.

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