Chemokine receptor expression by human intestinal epithelial cells

Abstract

Background & Aims: Intestinal epithelial cells produce an array of proinflammatory chemokines that can provide signals to mucosal immune and inflammatory cells. To determine if chemokines can also signal epithelial cells, we characterized the expression of chemokine receptors on human colon epithelial cells in vitro and in vivo. Methods: Expression of chemokine receptor messenger RNAs (mRNAs) by the human colon epithelial cell lines HT-29, HT-29.18.C1, Caco-2, T84, HCA-7, and LS174T was assessed by reverse-transcription polymerase chain reaction. Chemokine receptors on intestinal epithelial cells in vitro were determined by flow cytometry, and expression in vivo was determined by immunostaining of human colon. Interleukin (IL)-8 and growth-related (GRO) α secretion were assayed by enzyme-linked immunosorbent assay. Results: Human colon epithelial cells constitutively expressed mRNAs for an array of CC and CXC chemokine receptors, including CCR1-8 and CXCR4, but little if any CXCR1 or CXCR2. Further studies focused on CXCR4 and CCR5 because mRNA for those chemokine receptors was abundantly expressed by each of the colon epithelial cell lines, and these receptors were present on the cell surface. Analogous to their localization on polarized cell lines, CXCR4 and CCR5 had a predominant apical and, to a lesser extent, basolateral distribution on human enterocytes, as demonstrated by immunostaining of human colon. Human colon epithelial cells stimulated with stromal cell–derived factor 1α and macrophage inflammatory protein (MIP)- 1α or MIP-1β, which are the chemokine ligands for CXCR4 or CCR5, up-regulated production of the CXC chemokines IL-8 and GROα. Conclusions: Human colon epithelial cells express chemokine receptors. Human colonocytes have the potential to serve as targets for chemokine signaling.