TWEAK/Fn14 interaction stimulates human bronchial epithelial cells to produce IL-8 and GM-CSF.
TNF-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) family, is a multifunctional cytokine that regulates cellular proliferation, angiogenesis, inflammation, and apoptosis. In this study, we investigated the effect of TWEAK on human bronchial epithelial cells. A human bronchial epithelial cell line, BEAS2B, expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced IL-8 and GM-CSF upon TWEAK stimulation in a dose-dependent manner, which was abrogated by anti-Fn14 blocking antibody. TWEAK induced phosphorylation of IkappaBalpha and BAY11-7082, a selective inhibitor of IkappaBalpha phosphorylation, inhibited the TWEAK-induced IL-8 and GM-CSF production by BEAS2B cells. Moreover, primary cultured human bronchial epithelial cells also expressed Fn14 and produced IL-8 and GM-CSF upon TWEAK stimulation. Collectively, TWEAK stimulated human bronchial epithelial cells to produce IL-8 and GM-CSF through Fn14. Because IL-8 and GM-CSF are associated with inflammatory conditions, these results suggest that TWEAK/Fn14 interaction may play some roles in airway inflammatory responses.
Xu
Hongri
H
Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Okamoto
Atsushi
A
Ichikawa
Jiro
J
Ando
Takashi
T
Tasaka
Kachio
K
Masuyama
Keisuke
K
Ogawa
Hideoki
H
Yagita
Hideo
H
Okumura
Ko
K
Nakao
Atsuhito
A
D051017:Apoptosis Regulatory Proteins; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000074049:Cytokine TWEAK; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D020672:I-kappa B Proteins; D016209:Interleukin-8; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor