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1 Division of Pulmonary Disease and Critical Care Medicine, Departments of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
2 Department of Anatomy, Temple University School of Medicine, Philadelphia, PA, USA
3 Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: mark.aksoy{at}temple.edu.
We recently demonstrated that human bronchial epithelial cells (HBEC) constitutively express the chemokine receptor, CXCR3, which when activated, induces directed cell migration. The present study in HBEC examined the relative expression of the CXCR3 splice variants, CXCR3-A and CXCR3-B, cell-cycle dependence of CXCR3 expression, and the effects of the CXCR3 ligand, the interferon-
-inducible CXC chemokine, I-TAC/CXCL11, on DNA synthesis and cell proliferation. Both CXCR3-A and -B mRNA, assessed by real time RT-PCR, were expressed in normal HBEC (NHBEC) and the HBEC line, 16-HBE. However, CXCR3-B mRNA was 39- and 6-fold greater than CXCR3-A mRNA in NHBEC and 16-HBE, respectively. While most HBEC (>80%) assessed by flow cytometry and immunofluorescence microscopy contained intracellular CXCR3, only a minority (<40%) expressed it on the cell surface. In this latter subset of cells, most (>75%) were in the S + G2/M phases of the cell cycle. Stimulation of CXCR3 with I-TAC enhanced thymidine incorporation and cell proliferation and increased p38 and ERK1/2 phosphorylation. These data indicate that: 1) human airway epithelial cells primarily express CXCR3-B mRNA; 2) surface expression of CXCR3 is largely confined to the S + G2/M phases of the cell cycle; and 3) activation of CXCR3 induces DNA synthesis, cell proliferation and activation of MAP kinase pathways. We speculate that activation of CXCR3 exerts a mitogenic effect in HBEC, which may be important during airway mucosal injury in obstructive airway diseases such as asthma and COPD.
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