Faculty Collaboration Database

SDF-1/CXCL12 regulates cAMP production and ion transport in intestinal epithelial cells via CXCR4. Am J Physiol Gastrointest Liver Physiol 2004 May;286(5):G844-50

Date

12/20/2003

Pubmed ID

14684377

DOI

10.1152/ajpgi.00112.2003

Scopus ID

2-s2.0-1942519774 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

Human colonic epithelial cells express CXCR4, the sole cognate receptor for the chemokine stromal cell-derived factor (SDF)-1/CXC chemokine ligand (CXCL) 12. The aim of this study was to define the mechanism and functional consequences of signaling intestinal epithelial cells through the CXCR4 chemokine receptor. CXCR4, but not SDF-1/CXCL12, was constitutively expressed by T84, HT-29, HT-29/-18C1, and Caco-2 human colon epithelial cell lines. Studies using T84 cells showed that CXCR4 was G protein-coupled in intestinal epithelial cells. Moreover, stimulation of T84 cells with SDF-1/CXCL12 inhibited cAMP production in response to the adenylyl cyclase activator forskolin, and this inhibition was abrogated by either anti-CXCR4 antibody or receptor desensitization. Studies with pertussis toxin suggested that SDF-1/CXCL12 activated negative regulation of cAMP production through G(i)alpha subunits coupled to CXCR4. Consistent with the inhibition of forskolin-stimulated cAMP production, SDF-1/CXCL12 also inhibited forskolin-induced ion transport in voltage-clamped polarized T84 cells. Taken together, these data indicate that epithelial CXCR4 can transduce functional signals in human intestinal epithelial cells that modulate important cAMP-mediated cellular functions.

Author List

Dwinell MB, Ogawa H, Barrett KE, Kagnoff MF

Author

Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line
Chemokine CXCL12
Chemokines, CXC
Cyclic AMP
GTP-Binding Protein alpha Subunit, Gi2
GTP-Binding Protein alpha Subunits, Gi-Go
Humans
Intestinal Mucosa
Ion Transport
Proto-Oncogene Proteins
Receptors, CXCR4