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  3. Inducible Nitric Oxide Deficiency Attenuates Necroptosis in Psoriasis-like Dermatitis in Mice through Reducing Oxidative Stress

Inducible Nitric Oxide Deficiency Attenuates Necroptosis in Psoriasis-like Dermatitis in Mice through Reducing Oxidative Stress

  • J Invest Dermatol. 2025 Sep 15:S0022-202X(25)02428-5. doi: 10.1016/j.jid.2025.09.004.
Mengke Sun 1,  Pan Guo 2,  Qi Guo 1,  Hui Li 1,  Junkai Huang 1,  Jing Luo 1,  Qianyu Zhu 1,  Yufei Zhu 3,  Qianshu Yuan 1,  Sicheng Song 1,  Junchen He 4,  Long Su 5,  Weibin Xing 6,  Lizhi Hu 7
Affiliations

Affiliations

  • 1 Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China.
  • 2 Tianjin Pediatric Research Institute, Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin Children's Hospital (Children's Hospital of Tianjin University), No. 238 Longyan Road, Beichen District, Tianjin 300134, China.
  • 3 Natural Sciences, Mathematical and Physical Sciences Department, University College London (UCL), London, WC1E 6BT, UK.
  • 4 Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No. 354, Bei Road, Hongqiao District, Tianjin, 300120, China.
  • 5 Department of Ophthalmology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Orbital Disease, Tianjin, 300211, China.
  • 6 Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, No. 354, Bei Road, Hongqiao District, Tianjin, 300120, China. Electronic address: xingweibin111@163.com.
  • 7 Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, 300070, China; Department of Ophthalmology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Orbital Disease, Tianjin, 300211, China. Electronic address: lizhihu@tmu.edu.cn.
PMID: 40962201 DOI: 10.1016/j.jid.2025.09.004
Abstract

Psoriasis is a chronic inflammatory disease characterized by abnormal inflammatory responses and epidermal hyperplasia. In the inflammatory cascade of psoriasis, Necroptosis mediates inflammation-related keratinocyte death, which further amplifies both cell death and inflammation. In the present study, we demonstrated that inducible nitric oxide synthase (iNOS) deficiency attenuated the Necroptosis process by promoting clearance of Reactive Oxygen Species (ROS), consequently mitigating imiquimod-induced inflammatory infiltration and expression levels of inflammatory mediators. Following H2O2 stimulation in vitro, absence of iNOS significantly inhibited activation of necroptotic pathway in keratinocytes(KCs). In particular, topical application of nitric oxide (NO) not only inhibited the proliferation of KCs in psoriatic lesions, but significantly reduced the ROS levels and Necroptosis in KCs, which ultimately alleviated progression of psoriasis-like dermatitis. Collectively, these results suggest that NO can influence the pathogenesis of psoriasis-like dermatitis by modulating the necroptotic pathway in KCs. This study emphasizes the pivotal role of Necroptosis in the pathogenesis of psoriasis while providing insights for the development of iNOS/NO-based therapeutic strategies for psoriasis.

Keywords

Inflammation; Keratinocyte Necroptosis; Oxidative stress; Psoriasis; iNOS.

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