Cytoskeletal architecture differentially controls post-transcriptional processing of IL-6 and IL-8 mRNA in airway epithelial-like cells.
Airway epithelial cells are critically dependent on an intact cytoskeleton for innate defense functions. There are various pathophysiological conditions that affect the cytoskeletal architecture. We studied the effect of cytoskeletal distortion in polarized airway epithelial-like NCI-H292 cells on inflammatory gene expression, exemplified by interleukin(IL)-6 and IL-8. Disruption of microtubule structure with vinblastin and of actin with cytochalasin D did not affect TNF-alpha-induced IL-6 and IL-8 gene transcription but stabilized IL-8 and IL-6 mRNA. In line with previous studies, IL-8 mRNA stabilization was paralleled by hyperresponsive IL-8 production, but surprisingly, IL-6 production was reduced despite IL-6 mRNA stabilization. Polysome profiling revealed that, in cells with a disrupted cytoskeleton, translational efficiency of IL-6 mRNA was reduced, whereas that of IL-8 mRNA remained unaffected. Our findings indicate that distortion of the cytoskeleton in airway epithelial cells differentially affects both degradation and translation of IL-6 and IL-8 mRNA, modifying inflammatory gene expression and thus their innate defense function.
van den Berg
Arjen
A
Department of Pulmonology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.vandenberg@amc.uva.nl
Freitas
Jaime
J
Keles
Filiz
F
Snoek
Mieke
M
van Marle
Jan
J
Jansen
Henk M
HM
Lutter
René
R
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D047630:Depsipeptides / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
C083058:C-EPB transcription factor; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; D047630:Depsipeptides; D015850:Interleukin-6; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C057531:jasplakinolide; D018664:Interleukin-12; D003609:Dactinomycin; D015638:Cytochalasin D; D014747:Vinblastine; D017239:Paclitaxel