The STING antagonist H-151 ameliorates psoriasis via suppression of STING/NF-κB-mediated inflammation

Br J Pharmacol. 2021 Dec;178(24):4907-4922. doi: 10.1111/bph.15673. Epub 2021 Oct 30.


Background and purpose: Psoriasis is a chronic inflammatory skin disease associated with both innate and adaptive immune responses. The stimulator of interferon genes (STING) protein engages in sensing of cytosolic DNA to initiate dsDNA-driven immune responses. In vitro and in vivo anti-psoriasis effects of STING antagonist H-151 were explored.

Experimental approach: We analysed the gene expression profile of STING and related downstream targets in the skin samples of healthy people and psoriasis patients from the GEO database. Cellular inhibitory activity of H-151 on STING pathway was confirmed via qPCR and western blotting. The preventive effect of topical application of H-151 on imiquimod-induced psoriatic mice was examined through histological, immunohistochemical, immunofluorescent, flow cytometric analysis, ELISA Kits and other approaches. Preliminary mechanistic studies were also performed.

Key results: Gene expressions of STING and its downstream target were up-regulated in lesional skin samples from psoriasis patients. Topical administration of H-151 attenuated the skin lesions in imiquimod-induced psoriatic mouse model, while the secretion of pro-inflammatory cytokines (IL-17, IL-23 and IL-6), infiltration of M1 macrophages and differentiation of Th17 cells were significantly suppressed by H-151 treatment. Mechanistically, H-151 inhibited STING/NF-κB signalling in both keratinocytes and immune cells.

Conclusion and implications: H-151 displayed anti-inflammatory activity in both keratinocytes and immune cells, and decreased the severity of psoriatic response in vivo. Inhibition of STING signalling pathway may represent a novel therapeutic approach to psoriasis and related complications.

Keywords: IL-6; NF-κB; STING; antagonist; inflammation; psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Imiquimod / adverse effects
  • Inflammation / pathology
  • Keratinocytes
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B* / metabolism
  • Psoriasis* / drug therapy
  • Psoriasis* / pathology
  • Skin / metabolism


  • Cytokines
  • NF-kappa B
  • Imiquimod