Document Detail


CCR6 regulation of the actin cytoskeleton orchestrates human beta defensin-2- and CCL20-mediated restitution of colonic epithelial cells.
MedLine Citation:
PMID:  19233848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intestinal inflammation is exacerbated by defects in the epithelial barrier and subsequent infiltration of microbes and toxins into the underlying mucosa. Production of chemokines and antimicrobial peptides by an intact epithelium provide the first line of defense against invading organisms. In addition to its antimicrobial actions, human beta defensin-2 (HBD2) may also stimulate the migration of dendritic cells through binding the chemokine receptor CCR6. As human colonic epithelium expresses CCR6, we investigated the potential of HBD2 to stimulate intestinal epithelial migration. Using polarized human intestinal Caco2 and T84 cells and non-transformed IEC6 cells, HBD2 was equipotent to CCL20 in stimulating migration. Neutralizing antibodies confirmed HBD2 and CCL20 engagement to CCR6 were sufficient to induce epithelial cell migration. Consistent with restitution, motogenic concentrations of HBD2 and CCL20 did not induce proliferation. Stimulation with those CCR6 ligands leads to calcium mobilization and elevated active RhoA, phosphorylated myosin light chain, and F-actin accumulation. HBD2 and CCL20 were unable to stimulate migration in the presence of either Rho-kinase or phosphoinositide 3-kinase inhibitors or an intracellular calcium chelator. Together, these data indicate that the canonical wound healing regulatory pathway, along with calcium mobilization, regulates CCR6-directed epithelial cell migration. These findings expand the mechanistic role for chemokines and HBD2 in mucosal inflammation to include immunocyte trafficking and killing of microbes with the concomitant activation of restitutive migration and barrier repair.
Authors:
Rebecca A Vongsa; Noah P Zimmerman; Michael B Dwinell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-02-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-06     Completed Date:  2009-05-20     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10034-45     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism*
Animals
Caco-2 Cells
Cell Line, Tumor
Cell Movement
Cell Proliferation
Chemokine CCL20 / metabolism*
Chemokines / metabolism
Cytoskeleton / metabolism*
Gene Expression Regulation, Neoplastic*
Humans
Myosin Light Chains / metabolism
Rats
Receptors, CCR6 / metabolism*
beta-Defensins / metabolism*
Grant Support
ID/Acronym/Agency:
DK062066/DK/NIDDK NIH HHS; R01 DK062066/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/CCL20 protein, human; 0/CCR6 protein, human; 0/Chemokine CCL20; 0/Chemokines; 0/DEFB4A protein, human; 0/Myosin Light Chains; 0/Receptors, CCR6; 0/beta-Defensins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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