Abstract
BackgroundVasoactive intestinal peptide (VIP) exerts immune-modulatory actions mainly via VPAC1 receptor stimulation. VPAC1 may be a treatment target of inflammatory diseases, but little is known about the receptor expression profile in immune-competent cells in vivo.Material and methods20 male healthy subjects received a single intravenous bolus of 2ng/kg body weight Escherichia coli endotoxin (LPS). Receptor status was evaluated in peripherial blood cells before and 3, 6 and 24 h after LPS by FACS analysis and q-PCR. VIP plasma concentrations were measured by ELISA.ResultsGranulocytes accounted for 51% of leukocytes at baseline and 58 ± 37% were positive for VPAC1. The granulocyte population increased 2.6 fold after LPS, and a transient down-regulation of VPAC1 to 28 ± 23% was noted at 3 h (p < 0.001), which returned to baseline at 24 hours. Baseline VPAC1 expression was low in lymphocytes (6.3 ± 3.2%) and monocytes (11 ± 9.6%). In these cells, LPS up-regulated VPAC1 at 6 h (13.2 ± 4.9%, p < 0.001) and 24 h (31.6 ± 20.5%, p = 0.001), respectively. Consistent changes were noted for the VIP-receptors VPAC2 and PAC1. VPAC1, VPAC2 and PAC1 mRNA levels were unchanged in peripheral blood mononuclear cells (PBMC). VIP plasma concentration increased from 0.5 ± 0.3 ng/ml to 0.7 ± 0.4 ng/ml at 6 h after LPS (p < 0.05) and returned to baseline within 24 h.ConclusionThe time profile of VPAC receptor expression differs in granulocytes, monocytes and lymphocytes after LPS challenge in humans. Changes in circulating VIP concentrations may reflect innate immune responses.
Highlights
Vasoactive intestinal peptide (VIP) exerts immune-modulatory actions mainly via VPAC1 receptor stimulation
Granulocytes accounted for 51% of leukocytes at baseline and 58 ± 37% were positive for VPAC1
The granulocyte population increased 2.6 fold after LPS, and a transient down-regulation of VPAC1 to 28 ± 23% was noted at 3 h (p < 0.001), which returned to baseline at 24 hours
Summary
Vasoactive intestinal peptide (VIP) exerts immune-modulatory actions mainly via VPAC1 receptor stimulation. Down-regulation of tumor necrosis factor α (TNFα) [12], IL-6 [13], IL-8, IL-12 [14], inducible nitric oxide synthase (i-NOS) [15], and enhanced production of anti-inflammatory cytokines such as IL-10 and IL-1RN [16] have all been described to contribute to the direct anti-inflammatory action of VIP. These functions are mediated via three different Gprotein coupled receptors, VPAC1, VPAC2 and PAC1, which are localized on immune-competent cells and on other mesenchymal and endothelial tissues in humans [17,18,19,20]. Studies characterizing the expression of VPAC1 receptors on immune-competent cells and their regulation following immunological stimulation in humans are not available
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