L-Ascorbyl-2-phosphate attenuates NF-?B signaling in SZ95 sebocytes without affecting IL-6 and IL-8 secretion.

ABSTRACT: Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, L-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1?- or TNF-?-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-? was used as control. We also explored NF-?B activation which is known to orchestrate IL-1?- and TNF-?-mediated cytokine expression in many cell types. Both IL-1? and TNF-? increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1? induced IL-6 and IL-8 secretion. IL-1? but not TNF-? activated NF-?B canonical signaling as demonstrated by I?-B? phosphorylation and degradation as well as by nuclear accumulation of NF-?B/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1? and TNF-? on IL-6 and IL-8 gene expression as well as on IL-1?-mediated NF-?B signaling. In contrast, APS failed to reduce IL-1?-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1?-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1? on the inflammatory cytokine response and its molecular mechanisms in human sebocytes. Our data further suggest that the beneficial effect of APS in acne patients involves attenuation of NF-?B signaling but not reduction of IL-6 or IL-8 secretion.

SUBMITTER: Ikeno H 

PROVIDER: S-EPMC4540786 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature