Relative contribution of NF-kappaB and AP-1 in the modulation by curcumin and pyrrolidine dithiocarbamate of the UVB-induced cytokine expression by keratinocytes.
Following ultraviolet B treatment, expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 by NCTC 2544 keratinocyte cell line was significantly enhanced both at the mRNA and protein level. The UVB also increased the IL-10 steady-state mRNAs level. Radiation-induced cytokine overexpression was accompanied by NF-kappaB and AP-1 transcription factors activation as assessed by electrophoretic mobility shift assays. To investigate in keratinocytes the relative contributions of those transcription factors on UVB-mediated cytokine induction, cell cultures were supplemented with curcumin and pyrrolidine dithiocarbamate (PDTC), agents known to modulate NF-kappaB and AP-1 activation. Both compounds significantly inhibited NF-kappaB activation by UVB, but AP-1 activation was unaffected by curcumin while PDTC further stimulated its activation. In parallel, curcumin decreased, in a dose-dependent manner, the UVB-mediated overexpression of all three pro-inflammatory cytokines and only exhibited a moderate enhancing influence on IL-10 expression. In turn, the inhibitory influence of PDTC on radiation-induced TNF-alpha and IL-6 expression is much lower and in contrast to curcumin, it stimulated IL-8. Taken together, our data indicated that control of proinflammatory cytokine expression induced by UVB in keratinocytes required the selective inhibition of NF-kappaB activation. Simultaneous AP-1 activation by agents like PDTC might, partially or totally, depending on cytokine-type, counterbalanced the inhibitory effect exerted on UVB-induced NF-kappaB activation in keratinocytes.
Laboratoire d'Immunologie (EA2070), IFR 53 Biomolécules, INSERM, CNRS, 1 avenue du Maréchal Juin, 51100, Reims, France.
Alexia
A
Grandjean-Laquerriere
Sophie C
SC
Gangloff
Richard
R
Le Naour
Chantal
C
Trentesaux
William
W
Hornebeck
Moncef
M
Guenounou
D001483:Base Sequence; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D004247:DNA / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000528:radiation effects; D016328:NF-kappa B / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014466:Ultraviolet Rays
D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C020972:pyrrolidine dithiocarbamic acid; D004247:DNA; D003474:Curcumin