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-c 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.

Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity

“…In particular, the increase in PE is interesting as it was previously postulated that highly polyunsaturated PE can carry pro-inflammatory molecules such as the arachidonic acid lipid network [46]. Another phospholipid, phosphatidylinositol (PI), possesses immunoregulatory capacities [47]. Here we detect an increase in three PI species (PI 18:0/18:1, PI 18:1/16:0, PI 20:3/18:0) in centenarians.…”

Dysregulated phosphatidylinositol signaling promotes endoplasmic-reticulum-stress-mediated intestinal mucosal injury and inflammation in zebrafish

“…Its inactivation caused defects in B and T cell signaling and in bactericidal activity, resulting in chronic colitis in mice (Uno et al, 2010). Recently, PI itself has been shown to inhibit T cell proliferation and function, implicating it as a novel physiological immune suppressant (van Dieren et al, 2011). The μ-opioid receptor ligand DALDA, a compound that might activate PI3-K signaling, has been shown to protect glafenine-induced intestinal injury in zebrafish by ameliorating ER stress (Goldsmith et al, 2013).…”

Changes in Natural Foxp3+Treg but Not Mucosally-Imprinted CD62LnegCD38+Foxp3+Treg in the Circulation of Celiac Disease Patients

“…Immunohistochemical Foxp3 stainings were performed on paraffin-embedded duodenal biopsies as described previously [26]. Prior to staining the samples were blocked with 10% normal human serum in a solution containing Tris buffer (10 mM), EDTA (5 mM), NaCl (0.15 M), gelatine (0.25%) and Tween-20 (0.05%).…”

“…Tissue sections were incubated overnight using the primary antibody to Foxp3 (eBioscience) or isotype control mouse IgG 1 . Sections were incubated with VECTASTAIN ABC Elite Kit (Vector Laboratories) and stained with biotinylated horse-anti-mouse (Vector Laboratories) as described previously [26].…”