Acetyl-11-keto-β-boswellic acid inhibits the secretion of cytokines by dendritic cells via the TLR7/8 pathway in an imiquimod-induced psoriasis mouse model and in vitro

Life Sci. 2018 Aug 15:207:90-104. doi: 10.1016/j.lfs.2018.05.044. Epub 2018 May 31.

Abstract

Aims: Psoriasis vulgaris is mediated by T and dendritic cells. This study aimed to investigate the effects of acetyl-11-keto-β-boswellic acid (AKBA) on activated dendritic cells (DCs) using an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated with resiquimod (R848) in vitro.

Materials and methods: The mice were treated with IMQ and intragastrically administered 25-100 mg/kg/day of AKBA, 1 mg/kg/day of methotrexate (MTX), or normal saline. The inflammation of skin lesions in IMQ mice were evaluated by psoriasis area and severity index (PASI) and pathological staining. The related proteins of Toll-like receptor (TLR)7/8 pathways were assessed using Western blotting, and the expression levels of interleukin (IL)-23 and IL-12p40 mRNA using reverse transcription-polymerase chain reaction. The numbers of DCs and marker-positive BMDCs were assessed using flow cytometry and the levels of inflammatory factors using the enzyme-linked immunosorbent assay.

Key findings: AKBA and MTX obviously improved the psoriasis-like skin lesions of IMQ-treated mice. AKBA also obviously decreased the PASI score, reduced the thickness of epidermis, ameliorated the infiltration of CD3+ and CD11c+ cells in skin lesions, decreased the activation of local DCs, inhibited the mRNA expression and secretion of inflammatory factors IL-12 and IL-23, inhibited the maturation and differentiation of DCs to promote T-cell differentiation, and inhibited the activation of TLR7/8 and IRF signaling pathways.

Significance: This study implied that AKBA might have an anti-inflammatory effect on psoriasis by inhibiting the maturation and activation of DCs via the TLR8 and IRF signaling pathways.

Keywords: AKBA; BMDCs; IMQ-induced psoriasis-like; Psoriasis; R848- stimulated; TLR8.

MeSH terms

  • Aminoquinolines
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • Cell Differentiation
  • Cell Proliferation
  • Coculture Techniques
  • Cytokines / metabolism*
  • Dendritic Cells / metabolism
  • Erythema / metabolism
  • Imiquimod
  • Inflammation
  • Interleukin-12 Subunit p35 / metabolism
  • Interleukin-23 Subunit p19 / metabolism
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Spleen / metabolism
  • Toll-Like Receptor 7 / metabolism*
  • Toll-Like Receptor 8 / metabolism*
  • Triterpenes / chemistry*

Substances

  • Aminoquinolines
  • Cytokines
  • Il12a protein, mouse
  • Il23a protein, mouse
  • Interleukin-12 Subunit p35
  • Interleukin-23 Subunit p19
  • Membrane Glycoproteins
  • RNA, Messenger
  • TLR8 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Triterpenes
  • acetyl-11-ketoboswellic acid
  • Imiquimod