l-Ascorbyl-2-phosphate attenuates NF-κB 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-1β- or TNF-α-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-α was used as control. We also explored NF-κB activation which is known to orchestrate IL-1β- and TNF-α-mediated cytokine expression in many cell types. Both IL-1β and TNF-α increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1β induced IL-6 and IL-8 secretion. IL-1β but not TNF-α activated NF-κB canonical signaling as demonstrated by Iκ-Bα phosphorylation and degradation as well as by nuclear accumulation of NF-κB/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1β and TNF-α on IL-6 and IL-8 gene expression as well as on IL-1β-mediated NF-κB signaling. In contrast, APS failed to reduce IL-1β-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1β-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1β 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-κB signaling but not reduction of IL-6 or IL-8 secretion.Electronic supplementary materialThe online version of this article (doi:10.1007/s00403-015-1565-z) contains supplementary material, which is available to authorized users.

Topical erythritol combined with L-ascorbyl-2-phosphate inhibits staphylococcal growth and alleviates staphylococcal overgrowth in skin lesions of canine superficial pyoderma

“…In addition to its anti-inflammatory and antioxidant effects (Woolery-Lloyd et al 2010, Ikeno et al 2015, APS inhibited growth of staphylococci. mechanisms await elucidation.…”

“…Sodium suppresses inflammatory and oxidative reactions induced by UVB stimulation in the skin (Nayama et al 1999). Furthermore, it improves the solubility of the vitamin C derivative, L-ascorbyl-2-phosphate (APS), which is used to treat human acne vulgaris associated with Cutibacterium acnes (Ikeno et al 2015).…”

Endocrinology and immunology of acne: Two sides of the same coin

“…Complement C3, galectin-3-binding protein and neutrophil gelatinase-associated lipocalin were among the top 5 secreted sebocyte proteins [138] and the detection of demcidin expression in LA-treated human sebocytes [139] and the expression of NF-κB signalling induced by leptin through modification of sebaceous lipogenesis [140,141] indicate an important role of sebaceous glands in the innate immunity of the skin through the expression of antimicrobial peptides and specific lipids ( Figure 9). P. acnes does not only exhibit pro-inflammatory properties.…”

“…[ 135,136 ] An agonist peptide for the protease‐activated receptor‐2, which functions as innate biosensor for proteases expressed in sebaceous glands in acne, [ 128,137 ] enhanced lipogenesis and SREBP‐1 expression, induced cytokines and β‐defensin‐2 (hBD‐2) transcription in cultured sebocytes suggesting that a role of sebaceous glands in the immunological regulation of acne lesions. Complement C3, galectin‐3‐binding protein and neutrophil gelatinase‐associated lipocalin were among the top 5 secreted sebocyte proteins [ 138 ] and the detection of demcidin expression in LA‐treated human sebocytes [ 139 ] and the expression of NF‐κB signalling induced by leptin through modification of sebaceous lipogenesis [ 140,141 ] indicate an important role of sebaceous glands in the innate immunity of the skin through the expression of antimicrobial peptides and specific lipids (Figure 9).…”

Effect of Soy Isoflavones on the Improvement of Acne Vulgaris Severity by Reducing Tumor Necrosis Factor- Levels

“…In Indonesia, an estimated 15 million people suffer from AV between the ages of 13-40 [1]. Acne vulgaris is a dynamic and multifactorial process, involving four main factors, such as excess sebum production, hypercornification of the pilosebaceous ducts, inflammation caused by the colonization of Propionibacterium acnes (P. acnes), and microcome done caused by hyperkeratosis in the infundibulum of the pilosebaceous duct, corneocyte cohesion, and sebum secretion, pro-inflammatory cytokines IL-1, IL-8, and TNF- in the pathogenesis of AV [4][5][6].…”