期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 286, 期 5, 页码 G844-G850出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00112.2003
关键词
chemokine; chemokine receptors; G protein-coupled receptors; ion transport; adenosine 3 ',5 '-cyclic monophosphate; stromal cell-derived factor-1; CXC chemokine ligand; CXC receptor
资金
- NIDDK NIH HHS [DK-28305, DK-35108, DK-58960, K01 DK-02808, T32 DK-07202] Funding Source: Medline
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.
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