Metformin inhibits pro-inflammatory responses via targeting nuclear factor-κB in HaCaT cells

Abstract

Psoriasis is a prevalent, chronic inflammatory skin disease that arises from rapid and excessive growth of keratinocytes induced by abnormal inflammatory responses. Metformin is the first-line drug in type 2 diabetes and has been proven to possess significant anti-inflammatory effects in various diseases. In the present study, we examined the role of metformin in nuclear factor kappa B (NF-κB)-mediated inflammatory responses in HaCaT cells, a cell line for the keratinocyte. Our results demonstrated that metformin significantly decreased the mRNA and protein levels of tumour necrosis factor-α (TNFα), interleukin (IL)-6, IL-8, and IL-1β induced by TNFα. Immunofluorescence staining and western blot analysis showed that metformin inhibited the nuclear localization of p65, a subunit of nuclear factor NF-κB. In addition, metformin suppressed the transcription activity of NF-κB by inhibiting the degradation of IκBα. The inhibitory effect of metformin on NF-κB signalling is comparable with a specific IKKβ inhibitor BI605906. Collectively, our data suggest that metformin may be a potential therapeutic agent in inflammatory skin diseases like psoriasis.

Keywords: BI605906; metformin; nuclear factor-kappa B (NF-κB) signalling pathway; pro-inflammatory cytokines; psoriasis.