2. Academic Validation
  3. Alpha-7 nicotinic acetylcholine receptor agonist alleviates psoriasis-like inflammation through inhibition of the STAT3 and NF-κB signaling pathway

Alpha-7 nicotinic acetylcholine receptor agonist alleviates psoriasis-like inflammation through inhibition of the STAT3 and NF-κB signaling pathway

  • Cell Death Discov. 2022 Mar 30;8(1):141. doi: 10.1038/s41420-022-00943-4.
Yiwen Chen  # 1 2,  Panpan Lian  # 2,  Ziqi Peng 1,  Junaid Wazir 2,  Chujun Ma 1,  Lulu Wei 2,  Li Li 2,  Jun Liu 3,  Chen Zhao 2,  Wenyuan Pu 2,  Hongwei Wang 4,  Zhonglan Su 5
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P.R. China.
  • 2 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, P.R. China.
  • 3 Department of Dermatology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Nanjing, P.R. China.
  • 4 State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, P.R. China. [email protected].
  • 5 Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, P.R. China. [email protected].
  • # Contributed equally.
PMID: 35351863 DOI: 10.1038/s41420-022-00943-4
Abstract

Psoriasis is a chronic inflammatory cutaneous disease; it has been discovered that stimulation of the nervous system increases susceptibility to psoriasis. Although the cholinergic anti-inflammatory pathway, which is mediated by the alpha-7 nicotinic acetylcholine receptor (α7nAChR), is critical for controlling multiple types of inflammation, its expression pattern and pathogenesis function in psoriatic lesioned skin tissue are unknown. We hereby analyzed the expression of α7nAchR in human and mouse psoriatic skin tissue. In vivo, PNU-282987 or Methyllycaconitine, a specific agonist or antagonist of α7nAchR, were administered to imiquimod (IMQ)-induced psoriatic mouse models. The macroscopic appearance and histopathological features of the psoriatic mice skin were evaluated. In addition, cell proliferation and differentiation markers were investigated. The level of pro-inflammatory cytokines released from the lesioned skin, as well as the activation of the relevant signaling pathways, were measured. Our findings indicated that psoriatic lesional skin expressed an increased level of α7nAChR, with its tissue distribution being primarily in skin keratinocytes and macrophages. In an IMQ-induced murine psoriasis model, α7nAChR agonist PNU-282987 treatment alleviated psoriasis-like inflammation by down-regulating the expression of multiple types of pro-inflammatory mediators and normalized keratinocyte proliferation and differentiation, whereas α7nAChR antagonist treatment exacerbated its effect. Mechanically, we observed that activation of the α7nAChR inhibited the activation of the STAT3 and NF-κB signaling pathways in in vitro cultured HaCaT cells induced by Th17-related cytokine IL-6/IL-22 or Th1-related cytokine TNF-α. Taken together, these findings demonstrate that attenuation of psoriatic inflammation via the cholinergic anti-inflammatory pathway is dependent on α7nAChR activation.

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