Nacystelyn inhibits oxidant-mediated interleukin-8 expression and NF-kappaB nuclear binding in alveolar epithelial cells.
Nacystelyn (NAL), a recently developed lysine salt of N-acetyl-L-cytokine (NAC) has mucolytic and antioxidant properties. In this study, we investigated the effect of NAL upon oxidant-mediated interleukin (IL)-8 release and the activation of the redox-sensitive transcription factors AP-1, NF-kappaB, and C/EBP in a human alveolar epithelial cell line (A549). NAL (5 mM) enhanced intracellular glutathione (GSH) after 4 h and abolished H(2)O(2)-induced IL-8 release from A549 cells. This was associated with inhibition of NF-kappaB and C/EBP DNA-binding, measured by the Electrophoretic Mobility Shift Assay (EMSA). NAL also abolished the transcriptional activation of IL-8 in an IL-8-chloramphenicol acetyl transferase (CAT) reporter system, transfected into A549 cells. Supernatants obtained from H(2)O(2)-treated A549 cells induced chemotaxis of polymorphonuclear neutrophils, which could be inhibited by co-incubation with NAL. These data indicate that NAL may be used to modulate pro-inflammatory process by inhibiting cytokine release in the lungs and thus has therapeutic potential in inflammatory lung diseases.
Antonicelli
Frank
F
Department of Medical & Radiological Sciences, Respiratory Medicine Unit, ELEGI/Colt Research Laboratories, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, Scotland, UK.
Parmentier
Maryline
M
Drost
Ellen M
EM
Hirani
Nik
N
Rahman
Irfan
I
Donaldson
Ken
K
MacNee
William
W
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D011650:Pulmonary Alveoli / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; C086501:N-acetylcysteine lysinate; D016328:NF-kappa B; D016877:Oxidants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D008239:Lysine; D000111:Acetylcysteine