VIP/VPAC Axis Expression in Immune-Mediated Inflammatory Disorders: Associated miRNA Signatures

Abstract

Few studies have considered immune-mediated inflammatory disorders (IMID) together, which is necessary to adequately understand them given they share common mechanisms. Our goal was to investigate the expression of vasoactive intestinal peptide (VIP) and its receptors VPAC1 and VPAC2 in selected IMID, analyze the effect of biological therapies on them, and identify miRNA signatures associated with their expression. Serum VIP levels and mRNA of VPAC and miRNA expression in peripheral blood mononuclear cells were analyzed from 52 patients with psoriasis, rheumatoid arthritis, Graves’ disease, or spondyloarthritis and from 38 healthy subjects. IMID patients showed higher levels of VIP and increased expression of VPAC2 compared to controls (p < 0.0001 and p < 0.0192, respectively). Receiver operating characteristic curve analysis showed that the levels of VIP or VPAC2 expression were adequate discriminators capable of identifying IMID. Treatment of IMID patients with anti-TNFα and anti-IL12/23 significantly affected serum VIP levels. We identified miRNA signatures associated with levels of serum VIP and VPAC2 expression, which correlated with IMID diagnosis of the patients. The results indicate that the expression of VIP/VPAC2 is able of identify IMIDs and open up a line of research based on the association between the VIP/VPAC axis and miRNA signatures in immune-mediated diseases.

Effects of Neuropeptides on Dendritic Cells in the Pathogenesis of Psoriasis

“…One study examined the change of serum VIP level after treatment for immune mediated inflammatory diseases (including psoriasis and psoriatic arthritis) by biological agents and showed that TNF-α treatment can increase the level of serum VIP, while anti IL-12/23 treatment can reduce circulating VIP. 59 Another study found that narrowband ultraviolet B (NB-UVB) treatment had no significant effect on serum neuropeptide including SP, CGRP, brain-derived neurotrophic factor (BDNF), or corticotropin-releasing factor (CRF) levels. 64 As mentioned earlier, psoriasis symptoms can reappear.…”

“…A clinical experimental study observed that the plasma VIP level of the psoriasis group was significantly higher than that of the control group. 59 Immunohistochemical analysis showed that the number of VIP positive nerve fibers was significantly higher than that of psoriasis non lesional skin and healthy control skin. 4 VIP has different effects on DCs in various differentiation and stimulation states.…”