PSORI-CM02 formula alleviates imiquimod-induced psoriasis via affecting macrophage infiltration and polarization

Life Sci. 2020 Feb 15:243:117231. doi: 10.1016/j.lfs.2019.117231. Epub 2019 Dec 27.

Abstract

Aims: Psoriasis is a refractory skin disease characterized by macrophage cell infiltrated in the dermal layer. Macrophages can simultaneously polarize into two distinct functional subtypes, M1 and M2, and this process is affected by the microenvironment, cytokines and JAK/STAT pathways. Formula PSORI-CM02 is a novel Chinese medicine used to alleviate psoriasis symptoms and regulate T cell differentiation and epithelial cell proliferation. However, the effects of PSORI-CM02 in imiquimod (IMQ)-induced psoriasis and macrophage infiltration and polarization in the dermis remain unknown.

Main methods: Imiquimod induced psoriasis mice model and M1/M2 polarization model on mice peritoneal macrophages cell line RAW264.7 in vitro were used to observe the therapeutic effect of PSORI-CM02 on skin and its molecular mechanisms.

Key findings: PSORI-CM02 can significantly improve skin lesions and reduce macrophage infiltration in mice induced by imiquimod. After treatment with PSORI-CM02 formula, M1 macrophage mediators were significantly reduced, while M2 mediators were significantly increased in mice. Similarly in vitro, M1 macrophage proliferation was suppressed and M2 macrophage proliferation was elevated by PSORI-CM02 in the presence of LPS and IL-4, respectively. The elevated expression of TNF-α, iNOS, and IL-1β induced by LPS was reduced, while the expression of Arg-1, Fizz-1, Ym-1, and IL-10 induced by IL-4 was elevated in PSORI-CM02-treated cells. Finally, we found that the effects of PSORI-CM02 in macrophage polarization were associated with regulation of STAT1 and STAT6 expression, which were activated by LPS and IL-4, respectively.

Significance: Our novel findings reveal that PSORI-CM02 may possess therapeutic action in psoriasis treatment by regulating the infiltration and polarization of macrophages in the dermal layer.

Keywords: Inflammation; Macrophages; PSORI-CM02; Polarization; Psoriasis.

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Animals
  • Cell Differentiation
  • Cytokines / metabolism
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Imiquimod / adverse effects*
  • Macrophages / immunology*
  • Mice
  • Psoriasis / chemically induced
  • Psoriasis / immunology
  • Psoriasis / prevention & control*
  • RAW 264.7 Cells
  • RNA, Messenger / metabolism
  • Skin / drug effects
  • Skin / metabolism

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Drugs, Chinese Herbal
  • PSORI-CM01
  • RNA, Messenger
  • Imiquimod