Effects Of Niacinamide On TLRs-mediated Post-inflammatory Hyperpigmenation

BackgroundPost inflammatory hyperpigmentation (PIH) is concomitant with acne vulgaris and has become a major cosmetic concern in skin of color. As the roles of Prop ion ibacterium acnes (P. acnes) and its interaction with Toll like receptor2and4(TLR-2/4) on human keratinocytes have been well recognized in the pathogenesis of acne vulgaris, it is interesting to hypothesize that P. acnes and TLR-2/4signaling pathways could be involved in ace-related PIH.Niacinamide is a well-established effective anti-inflammatory and skin whitening agent in clinical use. However, its action has not been tested in the model of acne-related PIH which involves P. acnes and TLR-2/4signaling pathways, which may broaden our understanding of this classic pharmacological agent.ObjectiveThe present study was to investigate roles of P. acnes and its interactions with TLR2on human keratinocytes in the process of acne-related PIH and the actions of niacinamide against PIH.ResultsReal-time PCR found that mRNA expressions of IL-8and POMC were significantly elevated in both HaCaT cells when exposed to PGN, LTA and LPS, respectively. These findings were consistent with ELISA analysis. However, changes in IL-8and POMC production were not observed after TLR-2/4silencing. No significant difference was noted in PGNs from different origins. Interestingly, the pro-PIH process mediated by TLR-2/4activation could be inhibited in the presence of niacinamide as both IL-8and POMC productions were notably decreased. Moreover, this anti-PIH action of niacinamide demonstrated a dose-dependent manner. Niacinamide at the concentration of10μg/ml showed greatest inhibitory activity. These findings indicated that niacinamide could downregulate P. acnes-mediated PIH, at least partially via TLR-2/4signaling pathway.ConclusionsActivation of TLR-2/4could notably induce pro-inflammatory factors such as IL-8and pro-melanogenesis precursor POMC. However, these effects was not oberved in the presence of TLR-2/4silencer, suggesting TLR-2/4activation on keratinocytes is involved in PIH. As POMC has recently shown anti-inflammatory activities in response to stimuli, TLR-2/4-mediated PIH could be the result of the pro-and anti-inflammatory activities which simultaneously occur in vivo to maintain homeostasis. As TLR-2-induced cytokines showed no great differences despite the different origins of PGNs, the conclusion could be safely applied to P.acnes-induced PIH. However, TLR-2/4-mediated PIH could be downregulated by niacinamide in a dose-dependent manner. These findings could provide new insights into the molecular mechanisms of this classic pharmacological component.