title: Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells.
abstract: In addition to their role as regulators of leukocyte migration and activation, chemokines and their receptors also function in angiogenesis, growth regulation, and HIV-1 pathogenesis--effects that involve the action of chemokines on nonhematopoietic cells. To determine whether chemokine receptors are expressed in human colonic epithelium, HT-29 cells were examined by RT-PCR for the expression of the chemokine receptors for lymphotactin, fractalkine, CCR1-10, and CXCR1-5. The only receptor consistently detected was CXCR4 (fusin/LESTR), although HT-29 cells did not express mRNA for its ligand, stromal cell-derived factor (SDF-1alpha). Flow cytometric analysis with anti-CXCR4 antibody indicated that the CXCR4 protein was expressed on the surface of roughly half of HT-29 cells. CXCR4 was also expressed in colonic epithelial cells in vivo as shown by immunohistochemistry on biopsies from normal and inflamed human colonic mucosa. The mRNA for SDF-1alpha and other CC and CXC chemokines was present in normal colonic biopsies. The CXCR4 receptor in HT-29 cells was functionally coupled, as demonstrated by the elevation in [Ca2+]i, which occurred in response to 25 nM SDF-1alpha and by the SDF-1alpha-induced upregulation of ICAM-1 mRNA. Sodium butyrate downregulated CXCR4 expression and induced differentiation of HT-29 cells, suggesting a role for CXCR4 in maintenance and renewal of the colonic epithelium. This receptor, which also serves as a coreceptor for HIV, may mediate viral infection of colonic epithelial cells.
authors.affiliation: School of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom. N.J.Jordan@bath.ac.uk
authors.forename: N J
authors.initials: NJ
authors.lastname: Jordan
authors.forename: G
authors.initials: G
authors.lastname: Kolios
authors.forename: S E
authors.initials: SE
authors.lastname: Abbot
authors.forename: M A
authors.initials: MA
authors.lastname: Sinai
authors.forename: D A
authors.initials: DA
authors.lastname: Thompson
authors.forename: K
authors.initials: K
authors.lastname: Petraki
authors.forename: J
authors.initials: J
authors.lastname: Westwick
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D003106:Colon / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000235:genetics / Q000502:physiology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D020148:Butyric Acid; D018799:Intercellular Adhesion Molecule-1; D002118:Calcium