The chemokine CXCL16 is highly and constitutively expressed by human bronchial epithelial cells.
The chemokine receptor CXCR6 is highly expressed on lung-derived T cells compared to blood T cells, especially in inflammatory diseases characterised by T-cell migration to the lung. This suggests that CXCR6 is a candidate lung homing receptor. The sole ligand of CXCR6, CXCL16, has previously been shown to be expressed by alveolar macrophages. The authors hypothesized that also structural lung cells express CXCL16. CXCL16 expression was detected using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Chemotaxis assays were used to test functionality of the secreted protein. Human bronchial epithelial cells secreted relatively high basal levels of CXCL16 (> 1000 pg/mL). Interferon (IFN)-gamma, but not tumor necrosis factor (TNF)-alpha or interleukin (IL)-4, caused a modest but significant up-regulation in secretion. Airway smooth muscle and fibroblasts also expressed CXCL16, but at lower levels. Western blotting detected expression of the full-length (60-kDa) form of the chemokine in cell lysates, and the cleaved (35-kDa) form in culture supernatants. Concentrated supernatants from a bronchial epithelial cell line (BEAS-2B) were chemotactic for CXCR6 expressing T cells from blood. In conclusion, these results suggest that the bronchial epithelium is an important source of constitutively expressed CXCL16, which may be involved in T-cell recruitment to the lung in health and disease.
Institute for Lung Health, Department of Infection, Immunity and Inflammation, Glenfield Hospital, University of Leicester, Leicester, UK.
Caroline
C
Day
Rashmika
R
Patel
Cristina
C
Guillen
Andrew J
AJ
Wardlaw
D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D054427:Chemokine CXCL6 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D013601:T-Lymphocytes / Q000737:chemistry / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
C106330:CXCR6 protein, human; D054427:Chemokine CXCL6; D016207:Cytokines; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus