Roles of Vasoactive Intestinal Peptide (VIP) in the Expression of Different Immune Phenotypes by Wild-Type Mice and T Cell-Targeted Type II VIP Receptor Transgenic Mice

Abstract

Vasoactive intestinal peptide (VIP) and its two G protein-coupled receptors, VPAC1 and VPAC2, are quantitatively prominent and functionally critical in the immune system. Transgenic (T) mice constitutively expressing VPAC2 selectively in CD4 T cells, at levels higher than those found after maximal induction in CD4 T cells of wild-type (N) mice, have elevated blood concentrations of IgE, IgG1, and eosinophils; enhanced immediate-type hypersensitivity; and reduced delayed-type hypersensitivity. In contrast, VPAC2-null (K) mice manifest decreased immediate-type hypersensitivity and enhanced delayed-type hypersensitivity. The phenotypes are attributable to opposite skewing of the Th2/Th1 cytokine ratio, but no studies were conducted on the roles of T cell-derived VIP and altered expansion of the Th subsets. Dependence of the Th phenotype of T mice, but not of N or K mice, on T cell-derived VIP now is proven by showing that eliminating VIP from TCR-stimulated T cell cultures with VIPase IgG normalizes the elevated number of IL-4-secreting CD4 T cells, decreases the secretion of IL-4 and IL-10, and increases the secretion of IFN-γ. Flexible responsiveness of CD4 T cells from N and K mice, but not T mice, to exogenous VIP in vitro and in vivo is shown by increased numbers of IL-4-secreting CD4 T cells, greater secretion of IL-4 and IL-10, and lesser secretion of IFN-γ after TCR stimulation with VIP. The level of VIP recognized by CD4 T cells thus is a major determinant of the relative contributions of Th subsets to the immune effector phenotype.

Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: Altered expression and signal in immune cells

“…This is also supported by the fact that VPAC 1 is constitutively expressed in most immunocompetent cells; in addition, the notion of a role of VPAC 1 in VIP's effect on the inflammatory and Th1-driven responses and the generation of Treg cells has been supported by both in vitro and in vivo findings (2-4). However, studies using mice deficient in or transgenic for VPAC 2 have demonstrated the involvement of VPAC 2 only in a shift toward a Th2-prominent response (21)(22)(23), revealing a secondary role of this receptor in the regulation of autoimmunity by VIP. Accordingly, the present study shows that treatment with a VPAC 1 agonist, but not with a VPAC 2 agonist, reduces the frequency of arthritis, ameliorates symptoms, and prevents joint damage in an experimental model of arthritis.…”

Influence of bisfenol A on chemical coding of the nerve fibers of the cardiac apex in the domestic pig

“…Inną przyczyną różnic pomiędzy grupą kontrolną a zwierzętami poddanymi działaniu bisfenolu A mogła być prozapalna aktywność tej substancji. Jest to tym bardziej prawdopodobne, że w innych częściach układu nerwowego wpływ stanów zapalnych na neurochemiczną charakterystykę neuronów został stosunkowo dobrze poznany (36,41). W przypadku zapalenia zmiany w komórkach i włóknach nerwowych związane są zwykle z procesami adaptacyjnymi i neuroprotekcyjnymi, które mają za zadanie chronić układ nerwowy przed czynnikiem uszkadzającym tkanki (39,42).…”

Specific HIV gp120-cleaving Antibodies Induced by Covalently Reactive Analog of gp120

“…Evidence for increased potency because of the catalytic function has recently been published in regard to Ab antagonism of the biological effects of VIP, a 28-amino acid neuropeptide (32,33). Concerning gp120, a major hurdle has been to induce the synthesis of Abs that recognize the determinants involved in viral entry, i.e.…”