Vasoactive intestinal peptide (VIP) has potent antiproliferative and anti-inflammatory functions in the immune system. Two structurally distinct G-protein-associated receptors, VIP receptor type 1 (VPAC1) and VIP receptor type 2 (VPAC2), mediate the biological effects of VIP. The regulation of VIP receptor gene expression and the distribution of these receptors in different compartments of the human immune systems are unknown. This study reports, for the first time, a quantitative analysis of VPAC1 and VPAC2 mRNA expression in resting and activated T cells as well as in resting monocytes. Purified human peripheral blood CD4+ T cells and CD8+ T cells were stimulated via the TCR/CD3 receptor complex. Using the novel fluorometric-based kinetic (real-time) RT-PCR, we determined that VPAC1 is constitutively expressed in resting T cells and monocytes; the levels of expression were significantly higher in monocytes and CD4+ T cells than in CD8+ T cells. VPAC1 mRNA expression is significantly higher relative to VPAC2 in resting CD4+ T cells and CD8+ T cells. VPAC2 is expressed at very low levels in resting T cells but is not detectable in resting monocytes. In vitro stimulation of Th cells with soluble anti-CD3 plus PMA induced a T cell activation-dependent down-regulation of VPAC1. VPAC1 is down-regulated under conditions of optimal T cell stimulation. Our results suggest that selective VIP effects on T cell function may be mediated via selective expression of VPAC1 and VPAC2 on T cells and monocytes. Furthermore, down-regulation of VPAC1 in CD4+ T cell subpopulations is highly correlated with T cell activation.

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We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.

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The stimulated kallikrein activity assay allows differentiation of bradykinin- from histamine-mediated angioedema. The assay could feasibly be considered as a potential clinical tool for the diagnosis of bradykinin-mediated angioedema.

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Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to protect intestine from ischemia/reperfusion (I/R) injury in vivo and to down-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production in intestinal epithelial cells in vitro. The present study was undertaken to investigate whether HB-EGF could modulate the iNOS/NO axis after total midgut I/R injury in rats. I/R injury induced a significant increase in iNOS gene expression (quantified by real-time RT-PCR) and protein production (detected by western blots), as well as elevation of serum NO levels (measured by chemiluminescence assay). Nitrotyrosine (NT) and iNOS production colocalized immunohistochemically, with positive staining found mainly in villous and crypt epithelial cells, as well as ganglion cells. Intraluminal administration of HB-EGF 45 min after the start of a 90-min ischemic interval significantly decreased I/R-induced iNOS gene expression and protein production, as well as serum NO levels. Immunohistochemically, HB-EGF administration led to elimination of iNOS and NT staining in crypt epithelial cells and ganglion cells, with only weak staining that remained in villous epithelial cells. Thus, HB-EGF protects the intestine from I/R injury, at least partially, through down-regulation of the iNOS/NO/NT pathway, a mechanism that is central to I/R injury in multiple organ systems.