TY - JOUR
T1 - Novel association between vasoactive intestinal peptide and CRTH2 receptor in recruiting eosinophils
T2 - a possible biochemical mechanism for allergic eosinophilic inflammation of the airways
AU - El-Shazly, Amr E
AU - Begon, Dominique Y
AU - Kustermans, Gaelle
AU - Arafa, Mohammad
AU - Dortu, Estelle
AU - Henket, Monique
AU - Lefebvre, Philippe P
AU - Louis, Renaud
AU - Delvenne, Philippe
PY - 2013/1/11
Y1 - 2013/1/11
N2 - We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted in exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted in a significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1 cells was mediated through the CRTH2 receptor. Cell migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC-ε, PKC-δ, and PKA-α, -γ, and -IIαreg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils.
AB - We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted in exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted in a significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1 cells was mediated through the CRTH2 receptor. Cell migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC-ε, PKC-δ, and PKA-α, -γ, and -IIαreg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils.
KW - Amino Acid Sequence
KW - Base Sequence
KW - DNA Primers
KW - Enzyme-Linked Immunosorbent Assay
KW - Eosinophilia/metabolism
KW - Eosinophils/cytology
KW - Flow Cytometry
KW - Humans
KW - Hypersensitivity/metabolism
KW - Immunohistochemistry
KW - Molecular Sequence Data
KW - Receptors, Immunologic/metabolism
KW - Receptors, Prostaglandin/metabolism
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Trachea/metabolism
KW - Vasoactive Intestinal Peptide/chemistry
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UR - http://www.scopus.com/inward/citedby.url?scp=84872279890&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.422675
DO - 10.1074/jbc.M112.422675
M3 - Article
C2 - 23168411
SN - 0021-9258
VL - 288
SP - 1374
EP - 1384
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 2
ER -