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

Yuhang Li; Yitian Li; Sennan Xu; Yue Chen; Pan Zhou; Ting Hu; Hua Li; Ying Liu; Yaping Xu; Jie Ren; Yan Qiu; Canzhong Lu

doi:10.1016/j.phrs.2022.106491

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

Pharmacol Res. 2022 Nov:185:106491. doi: 10.1016/j.phrs.2022.106491. Epub 2022 Oct 13.

Authors

Yuhang Li¹, Yitian Li², Sennan Xu³, Yue Chen⁴, Pan Zhou⁵, Ting Hu¹, Hua Li⁶, Ying Liu³, Yaping Xu⁷, Jie Ren³, Yan Qiu⁸, Canzhong Lu⁹

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: yanqiu@xmu.edu.cn.
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: czlu@fjirsm.ac.cn.

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amidohydrolases
Animals
Dendritic Cells / metabolism
Enzyme Inhibitors / pharmacology
Inflammation
Interleukin-10*
Mice
Psoriasis* / drug therapy

Substances

N-acylethanolamines
Interleukin-10
Enzyme Inhibitors
Amidohydrolases