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Necessity for EFGR kinase enzymatic activity in the coordinate upregulation of a chemoattractant gene suite by vasoactive intestinal peptide in mouse lymphocytes (784.5)
Author(s) -
Saunders Jenna,
Wanjara Steve,
Hoselton Scott,
Schuh Jane,
Dorsam Glenn
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.784.5
Subject(s) - vasoactive intestinal peptide , chemotaxis , downregulation and upregulation , immune system , biology , cancer research , immunology , microbiology and biotechnology , neuropeptide , gene , receptor , biochemistry
Vasoactive intestinal peptide (VIP) is a potent chemoattractant for immune cells that is delivered by the peripheral nervous system to immune organs. However, the molecular mechanism regulating VIP’s chemoattractant properties is not known. Previously, our group published the VIP transcriptome in resting CD4 T cells, which identified a chemoattractant gene set (e.g. EGFR, Snail and syt XIII) that was coordinately upregulated. We hypothesize that these gene products control the chemoattractant activity of VIP in immune cells. Moreover, we propose that this chemoattractant gene set is transcriptionally upregulated by the transactivation of EGFR by VIP as is observed in non‐immune cells, including breast and colon cancer cells. This research will utilize primary mouse splenocytes treated +/‐ VIP over various time intervals in an attempt to identify which FACS‐sorted splenocyte subpopulations are sensitive to VIP and the extent to which the chemoattractant gene set is upregulated. Optimal conditions will be repeated +/‐ EGFR neutralizing antibody or a specific EGFR kinase inhibitor to assess the contribution of EGFR enzymatic activity for the chemoattractant gene expression changes. Lastly, Boyden‐chamber chemotaxis assays will be employed to test whether pharmacological inhibition against EGFR kinase activity and/or other chemoattractant gene products suppresses VIP’s chemoattractant activity using identified splenocyte subpopulations. The significance of the proposed research is to better understand the molecular control of lymphocyte trafficking mediated by the nervous system. Grant Funding Source : This research was supported by NIH/NIAID (R15 to GD).