Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells

J Clin Invest. 1999 Oct;104(8):1061-9. doi: 10.1172/JCI6685.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyric Acid / pharmacology
  • Calcium / metabolism
  • Chemokine CXCL12
  • Chemokines, CXC / physiology
  • Colon / chemistry*
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • RNA, Messenger / analysis
  • Receptors, CXCR4 / analysis*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / physiology


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • RNA, Messenger
  • Receptors, CXCR4
  • Butyric Acid
  • Intercellular Adhesion Molecule-1
  • Calcium