p38 MAPK and NF-kappaB on IL-6 release in human gingival fibroblasts.
The induction of interleukin-6 (IL-6) using a proinflammatory cytokine (IL-1beta) was studied in human gingival fibroblasts (HGFs) in relation to p38 MAPK and NF-kappaB transcription factor. When added to HGFs, IL-1beta had a stimulatory effect on the production of IL-6, and this effect was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release also was reduced by the addition of pyrrolidine dithiocarbamate or NF-kappaB SN50, which has been reported as potent NF-kappaB inhibitor. Both the NF-kappaB inhibitors in the presence of SB203580 had more inhibitory effect on IL-6 release. IL-13 stimulated NF-kappaB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on the NF-kappaB activation, and both the NF-kappaB inhibitors failed to reduce the p38 MAPK activation in the IL-1beta-stimulated HGFs. These results strongly suggest that both p38 MAPK and NF-kappaB are required in IL-1beta-induced IL-6 synthesis and that these two IL-1beta-activated pathways can be primarily dissociated.
Chae
H J
HJ
Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju, South Korea.
Byun
J O
JO
Chae
S W
SW
Kim
H M
HM
Choi
H I
HI
Pae
H O
HO
Chung
H T
HT
Kim
H R
HR
D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D010455:Peptides; D011725:Pyridines; D011759:Pyrrolidines; D012333:RNA, Messenger; C118258:SN50 peptide; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580