The chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells.
Activation of the chemokine receptor CXCR3 by its cognate ligands induces several differentiated cellular responses important to the growth and migration of a variety of hematopoietic and structural cells. In the human respiratory tract, human airway epithelial cells (HAEC) release the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. Simultaneous expression of CXCR3 by HAEC would have important implications for the processes of airway inflammation and repair. Accordingly, in the present study we sought to determine whether HAEC also express the classic CXCR3 chemokine receptor CXCR3-A and its splice variant CXCR3-B and hence may respond in autocrine fashion to its ligands. We found that cultured HAEC (16-HBE and tracheocytes) constitutively expressed CXCR3 mRNA and protein. CXCR3 mRNA levels assessed by expression array were approximately 35% of beta-actin expression. In contrast, CCR3, CCR4, CCR5, CCR8, and CX3CR1 were <5% beta-actin. Both CXCR3-A and -B were expressed. Furthermore, tracheocytes freshly harvested by bronchoscopy stained positively for CXCR3 by immunofluorescence microscopy, and 68% of cytokeratin-positive tracheocytes (i.e., the epithelial cell population) were positive for CXCR3 by flow cytometry. In 16-HBE cells, CXCR3 receptor density was approximately 78,000 receptors/cell when assessed by competitive displacement of 125I-labeled IP-10/CXCL10. Finally, CXCR3 ligands induced chemotactic responses and actin reorganization in 16-HBE cells. These findings indicate constitutive expression by HAEC of a functional CXC chemokine receptor, CXCR3. Our data suggest the possibility that autocrine activation of CXCR3 expressed by HAEC may contribute to airway inflammation and remodeling in obstructive lung disease by regulating HAEC migration.
Kelsen
Steven G
SG
Division of Pulmonary Disease and Critical Care Medicine, Departments of Medicine, Philadelphia, PA 19140, USA. Kelsen@temple.edu
Aksoy
Mark O
MO
Yang
Yi
Y
Shahabuddin
Syed
S
Litvin
Judith
J
Safadi
Fayez
F
Rogers
Thomas J
TJ
D017398:Alternative Splicing; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D007457:Iodine Radioisotopes; D011014:Pneumonia / Q000378:metabolism / Q000503:physiopathology; D011869:Radioligand Assay; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology*
C515187:CXCR3 protein, human; D007457:Iodine Radioisotopes; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine