Differential effects of PKC inhibitors on gelatinase B and interleukin 6 production in the mouse macrophage.
Pretreatment of LPS-induced RAW 264.7 cells with three PKC inhibitors suggests that induction of TNF-alpha, nitric oxide (NO), gelatinase B (Gel B) and IL-6 involves at least three distinct signalling pathways. We confirmed the PKC dependence of TNF-alpha and NO productions and found that Gel B was inhibited by Calphostin C (CAL), but potentiated by staurosporine (STAR) and CGP 41 251. IL-6 production was stimulated by the three inhibitors. Our results indicate that up-regulation of Gel B, TNF-alpha and NO seems to involve PKC at different levels, whereas up-regulation of IL-6 production appears to be PKC-independent. However, IL-6 production in RAW 264.7 cells seems to be down-regulated by a PKC-dependent feedback mechanism.
Tremblay
P
P
Centre de recherches en immunologie, Institut Armand-Frappier, Laval, Que, Canada.
Houde
M
M
Arbour
N
N
Rochefort
D
D
Masure
S
S
Mandeville
R
R
Opdenakker
G
G
Oth
D
D
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D017364:Collagenases / Q000032:analysis / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D051379:Mice; D009281:Naphthalenes; D009569:Nitric Oxide / Q000096:biosynthesis; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019311:Staurosporine / Q000031:analogs & derivatives; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000470:Alkaloids; D015850:Interleukin-6; D009281:Naphthalenes; D011083:Polycyclic Compounds; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011493:Protein Kinase C; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D019311:Staurosporine; C058819:calphostin C; C059539:midostaurin