Subcellular expression pattern and role of IL-15 in pneumococci induced lung epithelial apoptosis.
Streptococcus pneumoniae is the leading causative agent of community-acquired pneumonia. Induction of apoptosis in pulmonary epithelial cells by bacteria during pneumonia might be harmful to the host. Interleukin-15 (IL-15) has been demonstrated as an effective inhibitor of apoptosis and is expressed in lung epithelium on the mRNA and protein level. Therefore, we characterized the sub-cellular expression pattern of the short and long IL-15 isoforms in lung epithelial cells in vitro as well as its role in pneumococci-related lung epithelial cell apoptosis. We found an expression pattern for both IL-15 signal peptides in the pulmonary epithelial cell lines A549 and Beas-2B. Moreover, a strong co-localization of IL-15 and IL-15Ralpha was detected on cell surfaces. Compared to pro-inflammatory cytokine stimulation, neither IL-15 nor its trimeric receptor complex was up-regulated after pneumococcal infection. However, overexpression of IL-15 isoforms revealed IL-15LSP and IL-15Vkl as inhibitors of pneumococci induced apoptosis in pulmonary epithelial cells. Thus, IL-15 may act as an anti-apoptotic molecule in pneumococci infection, thereby suggesting IL-15 as a benefical cytokine in pulmonary host defense against infection.
Hocke
Andreas C
AC
Department of Internal Medicine/Infectious and Pulmonary Diseases, Charité, Universitätsmedizin Berlin, 13353, Berlin, Germany. andreas.hocke@charite.de
Hartmann
Ines K
IK
Eitel
Julia
J
Optiz
Bastian
B
Scharf
Stefanie
S
Suttorp
Norbert
N
Hippenstiel
Stefan
S
D017209:Apoptosis; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014162:Transfection
C508024:IL15RA protein, human; D019409:Interleukin-15; D020033:Protein Isoforms; D053647:Receptors, Interleukin-15