VIP Signaling Fails to Alter Gene Expression but Induces Different [cAMP]i Responses in Human Malignant Hut-78 and Molt-4 T Cell Lines; Implications for Different G-protein Coupling for VIP Receptors

Author(s): Travis V.-D. Steen, Manpreet Bains, Steve Wanjara, Brittany Bisnett, Caleb Laney, Ben Huber, Sheri T. Dorsam, Jane M. Schuh, Glenn P. Dorsam*.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)
(Formerly Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents)

Volume 16 , Issue 3 , 2016

Graphical Abstract:


Background: Vasoactive intestinal peptide (VIP) is a 3.3 kDa pleiotropic protein with a broad expression profile that displays immune modulating activities. VIP binds two G protein-coupled receptors called Vasoactive Intestinal Pepide/Pituitary Adenylate Cyclase activating polypeptide receptor (VPAC) 1 and 2 that elicit multiple downstream signaling molecules, including adenylate cyclase. VIP differentially regulates over 300 genes in resting and activated murine CD4 T cells, and is chemotactic to resting and Th2 effector T cells.

Objective: This study is focused on delineating which human VIP receptor, called VPAC1 and VPAC2, controls T cell biology pertaining to gene expression, signaling and chemotaxis.

Method: To this end, we utilized human T cell lines known to exclusively express VPAC1, (HuT-78) or VPAC2 (Molt-4) in an attempt to identify VIP-receptor mediated changes in gene expression, signaling and chemotaxis.

Results: This research successfully demonstrated three major findings. First, malignant or primary human T cells failed to differentially regulate any gene targets when treated with VIP ligand as assessed by an Agilent whole human microarray. Second, despite drastically different [cAMP]i profiles, both T cell lines responded similarly to VIP in Boyden Chamber assays showing both chemorepulsion and chemoattraction at low versus high VIP concentrations. Lastly, both T cell lines were equally sensitive to AC and PKA inhibitors that blocked VIP-induced chemotaxis, but were differentially sensitive to PKC inhibitors.

Conclusion: Collectively, these results indicate that VIP signaling in resting human T cells is ineffective at altering mRNA expression changes, unlike their rodent counterparts, but can influence similar chemotactic effects, possibly through different signaling pathways elicited through VPAC1 versus VPAC2.

Keywords: cAMP, chemotaxis, gene expression, signaling, T cells, vasoactive intestinal peptide.

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Article Details

Year: 2016
Page: [178 - 198]
Pages: 21
DOI: 10.2174/1871522217666170206152357
Price: $58

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