Chemokine receptor expression by human intestinal epithelial cells

Background & Aims: Intestinal epithelial cells produce an array of proinfla mmatory chemokines that can provide signals to mucosal immune and inflammat ory cells. To determine if chemokines can also signal epithelial cells, we characterized the expression of chemokine receptors on human colon epitheli al cells in vitro and in vivo. Methods: Expression of chemokine receptor me ssenger 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 ce lls 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) alpha secretion were assayed by enzyme-linked immunosorbent a ssay. 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 CCR 5 because mRNA for those chemokine receptors was abundantly expressed by ea ch 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, basolatera l distribution on human enterocytes, as demonstrated by immunostaining of h uman colon. Human colon epithelial cells stimulated with stromal cell-deriv ed factor 1 alpha and macrophage inflammatory protein (MIP)-1 alpha or MIP- 1 beta, which are the chemokine ligands for CXCR4 or CCR5, up-regulated pro duction of the CXC chemokines IL-8 and GRO alpha. Conclusions: Human colon epithelial cells express chemokine receptors. Human colonocytes have the po tential to serve as targets for chemokine signaling.