Interference with IL-13/JAK1/STAT6 inflammatory signaling by dipalmitoyl phosphoethanolamine-polyethylene glycol (DPPE-PEG); A CD1d-dependent antagonist to iNKT cells; contributes to retarding the advancement of oxazolone colitis.

Ulcerative colitis-associated immune dysregulation necessitates an appropriate and effective therapy to suppress its progression and achieve sustained remission. The current research was designed to examine the prospective anti-colitis mechanism of dipalmitoyl phosphoethanolamine-polyethylene glycol (DPPE-PEG); a CD1d-dependent antagonist to invariant natural killer T (iNKT) cells with previously reported potent anti-inflammatory activity. Colitis was induced in BALB/c mice by cutaneous pre-sensitization with 3% oxazolone, followed 5 days later by intra-colonic injection of 1% oxazolone to evaluate the therapeutic effect of DPPE-PEG (250 μg; i.p.). DPPE-PEG substantially ameliorated the decrease in body weight, disease activity index (DAI), histological alterations induced by oxazolone, and almost normalized colon length. Our findings revealed that DPPE-PEG down-regulated CD1d expression. In addition, DPPE-PEG greatly attenuated the colonic inflammatory response and apoptosis, that was evidenced by significantly diminished colon myeloperoxidase (MPO) activity, interleukin-13 (IL-13) and tumor necrosis factor-alpha (TNF-α) contents, along with down-regulated relative protein expressions of p-JAK1 (phosphorylated-Janus kinase 1) and phosphorylated-signal transducer and activator of transcription 6 (p-STAT6), as well as the pro-apoptotic Bax and the apoptotic effector cleaved caspase-3. Collectively, the interference of DPPE-PEG with iNKT cells activation evidenced by reduced CD1d expression and IL-13 cytokine, with subsequently retarded activation of JAK1/STAT6 inflammatory signaling and preserved intestinal mucosa could, at least partly, contribute to impeding the progression of colitis. These findings reinforce our suggestion that DPPE-PEG could be an effective and promising candidate for retarding the advancement of ulcerative colitis.