2. Academic Validation
  3. N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation

N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation

  • Pharmacol Res. 2022 Oct 13;106491. doi: 10.1016/j.phrs.2022.106491.
Yuhang Li 1,  Yitian Li 2,  Sennan Xu 3,  Yue Chen 4,  Pan Zhou 5,  Ting Hu 1,  Hua Li 6,  Yin Liu 3,  Yaping Xu 7,  Jie Ren 3,  Yan Qiu 8,  Canzhong Lu 9
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, China; Xiamen Institute of Rare-earth Materials, Haixi Institutes, Chinese Academy of Sciences, Fujian, 361005, China.
  • 2 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China; Department of Clinical Pharmacy, The Third Hospital of Mianyang/Sichuan Mental Health Center, Mianyang, 621000, Sichuan, China.
  • 3 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China.
  • 4 Department of Dermatology, The Eighth Affiliated Hospital of SUN YAT-SEN University, Shenzhen 518033, Guangdong, China.
  • 5 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China; Department of Pathology, Qilu Hospital, Shandong University, Jinan, 250012 China.
  • 6 The Department of Science and Education, The Second Affiliated Hospital of Xiamen Medical college, Xiamen, China.
  • 7 Institute of Respiratory Diseases Xiamen Medical College; Xiamen, Fujian, 361002, China; Key laboratory of functional and clinical translational medicine, Fujian province university, Xiamen Medical College; Xiamen, Fujian, 361002, China.
  • 8 Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
  • 9 CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, China; Xiamen Institute of Rare-earth Materials, Haixi Institutes, Chinese Academy of Sciences, Fujian, 361005, China. Electronic address: [email protected].
PMID: 36244543 DOI: 10.1016/j.phrs.2022.106491
Abstract

Psoriasis is an incurable autoimmune disease that affects 2-3% of the world's population. Limited understanding of its pathogenesis hinders the development of therapies for the disease. Herein, we reported that N-acylethanolamine acid amidase (NAAA), a cysteine Enzyme that catalyzes the hydrolysis of fatty acid ethanolamides (FAEs), was upregulated in psoriasis patients and imiquimod (IMQ)-induced mouse model of psoriasis. The upregulated NAAA contributes to the progression of psoriasis via enhancing dendritic cell (DCs) maturation. Transgenic expression of NAAA in mice accelerated the development of psoriasis, whereas genetic ablation of NAAA or local administration of NAAA inhibitor F96 ameliorated psoriasis. NAAA expressed in dendritic cells (DCs), but not in macrophages, T cells, or keratinocytes plays a critical role in psoriasis development. In addition, the results showed that NAAA degrades palmitoylethanolamide (PEA) and reduces PEA-PPARα-mediated dissociation of NF-κB p65 from Sirtuin 1 (SIRT1), subsequently, repressing the acetylation of p65 and down-regulating IL10 production. The decreased IL10 then leads to the maturation of DCs, thus promoting the development of psoriasis. These results provide new insights into the pathophysiological mechanism of psoriasis and identify NAAA as a novel target for the treatment of psoriasis.

Keywords

Dendritic cells (DCs); N-Acylethanolamine acid amidase (NAAA); Palmitoylethanolamide (PEA); Peroxisome proliferator activated receptor α (PPARα); Psoriasis; Sirtuin 1 (SIRT1).

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