Mechanisms involved in ultrafine carbon black-induced release of IL-6 from primary rat epithelial lung cells.
The aims of the present study were to establish to what extent IL-1, and intracellular pathways involving mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB), play a role in ultrafine particle-induced release of IL-6 by primary rat epithelial lung cells. Ultrafine carbon black (Printex 90) induced a concentration- and time-dependent increase in the release of IL-1alpha, IL-1beta and IL-6. The ultrafine carbon black-induced release of IL-6 was completely eliminated by an IL-1 receptor antagonist (IL-1ra). Cellular release of IL-1alpha, IL-1beta and IL-6 was significantly attenuated by curcumin and by inhibitors of the MAPKs ERK1/2 (PD98069), p38 (SB202190) and JNK (SP600125), whereas pyrrolidine dithiocarbamate (PDTC) attenuated the release of IL-6, but not of IL-1alpha and IL-1beta. The effects of curcumin and PDTC may indicate an involvement of NF-kappaB. Furthermore, ultrafine carbon black induced degradation of IkappaBalpha, used as an indicator of NF-kappaB activation, and induced phosphorylation of ERK1/2, p38 and JNK1/2. This degradation and phosphorylation was attenuated by IL-1ra. The present findings provide more insight into the largely unknown mechanisms involved in ultrafine particle-induced release of cytokines from lung cells. The findings suggest that ultrafine carbon black-induced release of IL-6 strongly depends on IL-1 and that activation of MAPKs and NF-kappaB is involved in this response.
Totlandsdal
Annike I
AI
Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. annike.irene.totlandsdal@fhi.no
Refsnes
Magne
M
Låg
Marit
M
D000818:Animals; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D052638:Particulate Matter; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D053260:Soot / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016207:Cytokines; D007202:Indicators and Reagents; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D016328:NF-kappa B; D052638:Particulate Matter; D012333:RNA, Messenger; D053260:Soot; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases