Inhibitory effects of superoxide dismutase 3 on Propionibacterium acnes-induced skin inflammation

Cuong Thach Nguyen,Christos C Zouboulis,Shyam Kishor Sah,Tae-Yoon Kim

doi:10.1038/s41598-018-22132-z

Abstract

Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on P. acnes- or peptidoglycan (PGN)-induced inflammation in vitro and in vivo. Our data demonstrated that SOD3 suppressed toll-like receptor-2 (TLR-2) expression in P. acnes- or PGN-treated keratinocytes and sebocytes. Moreover, we found that SOD3 suppressed the expressions of phosphorylated nuclear factor-κB (NF-κB) and p38 in P. acnes- or PGN-treated cells. SOD3 also exhibited an anti-inflammatory role by reducing the expression of inflammasome-related proteins (NLRP3, ASC, caspase-1) and inhibiting the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8. In addition, SOD3 reduced lipid accumulation and expression of lipogenic regulators in P. acnes-treated sebocytes. Recombinant SOD3-treated wild-type mice and SOD3 transgenic mice, which were subcutaneously infected with P. acnes, showed tolerance to inflammation through reducing inflammatory cell infiltration in skin, ear thickness, and expression of inflammatory mediators. Our result showed that SOD3 could suppress the inflammation through inhibition of TLR2/p38/NF-κB axis and NLRP3 inflammasome activation. Therefore, SOD3 could be a promising candidate for treatment of P. acnes-mediated skin inflammation.

Highlights

Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease
We examined whether P. acnes or peptidoglycan (PGN control) activated toll-like receptor-2 (TLR-2) and its downstream nuclear factor-κB (NF-κB) signaling in HaCaT and SZ95 cells
We found that superoxide dismutase 3 (SOD3) significantly decreased the expression of TLR-2 at the mRNA (Fig. 1A) and protein levels (Figs 1B and S1C,S5A) in both cells

Summary

Introduction

Propionibacterium acnes is a well-known commensal bacterium that plays an important role in the pathogenesis of acne and chronic inflammatory skin disease. SOD3 reduces IL-23-mediated skin inflammation by inhibiting activation of immune responses and by suppressing infiltration of immune cells in mice[17]. SOD3 suppresses hypoxia-induced expression of angiogenic factors and pro-inflammatory cytokines through down-regulation of HIF-1α, PKC, and NF-κB signaling in vitro and in vivo[19]. These results showed that SOD3 has an important role in inflammatory diseases and this led us to investigate the role of SOD3 in P. acnes-induced skin inflammation. SOD3 suppressed the expressions of p-NF-κB, p-p38, inflammasome proteins (NLRP3, ASC, and caspase-1), and inflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-8 in P. acnes- or PGN-treated keratinocytes and sebocytes. Treatment with SOD3 significantly inhibited P. acnes-induced skin inflammation including ear thickness, erythema, and infiltration of inflammatory cells, suggesting that SOD3 has anti-inflammatory effects in P. acnes-induced acne vulgaris

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