{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:54:24Z","timestamp":1793220864257,"version":"4.5.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union\u2014NextGenerationEU","award":["PNRR M4C2-Investimento 1.4-CN00000041-PNRR_CN3RNA_SPOKE9"],"award-info":[{"award-number":["PNRR M4C2-Investimento 1.4-CN00000041-PNRR_CN3RNA_SPOKE9"]}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["2022NLLBWT"],"award-info":[{"award-number":["2022NLLBWT"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["2022J5ZL4B"],"award-info":[{"award-number":["2022J5ZL4B"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["DA 9158"],"award-info":[{"award-number":["DA 9158"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Intestinal fibrosis, a frequent complication of inflammatory bowel disease, is characterized by stricture formation with no pharmacological treatment to date. N-acylethanolamine acid amidase (NAAA) is responsible for the hydrolysis of acylethanolamides (AEs, eg, palmitoylethanolamide and oleoylethanolamide). Here, we investigated NAAA and AE signaling in gut fibrosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>NAAA and AE signaling were evaluated in human intestinal specimens from patients with stenotic Crohn\u2019s disease (CD). Gut fibrosis was induced by 2,4,6-trinitrobenzenesulfonic acid, monitored by colonoscopy, and assessed by qRT-PCR, histological analyses, and confocal microscopy. Immune cells in mesenteric lymph nodes were analyzed by FACS. Colonic fibroblasts were cultured in conditioned media derived from polarized or non-polarized bone marrow-derived macrophages (BMDMs). IL-23 signaling was evaluated by qRT-PCR, ELISA, FACS, and western blot in BMDMs and in lamina propria CX3CR1+ cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In ileocolonic human CD strictures, increased transcript expression of NAAA was observed with a decrease in its substrates oleoylethanolamide and palmitoylethanolamide. NAAA inhibition reduced intestinal fibrosis in vivo, as indicated by a decrease in inflammatory parameters, collagen deposition, and fibrosis-related genes, including those involved in epithelial-to-mesenchymal transition. More in-depth studies revealed modulation of the immune response related to IL-23 following NAAA inhibition. The antifibrotic actions of NAAA inhibition are mediated by M\u03c6 and M2 macrophages that indirectly affect fibroblast collagenogenesis. NAAA inhibitor AM9053 normalized IL-23 signaling in BMDMs and in lamina propria CX3CR1+ cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings provide new insights into the pathophysiological mechanism of intestinal fibrosis and identify NAAA as a promising target for the development of therapeutic treatments to alleviate CD-related fibrosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae132","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T11:29:52Z","timestamp":1724844592000},"source":"Crossref","is-referenced-by-count":8,"title":["Pharmacological Inhibition of <i>N<\/i>-Acylethanolamine Acid Amidase (NAAA)\u00a0Mitigates Intestinal Fibrosis Through Modulation of Macrophage Activity"],"prefix":"10.1093","volume":"19","author":[{"given":"Maria Francesca","family":"Nan\u00ec","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Pagano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"De Cicco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lucariello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Paola","family":"Tropeano","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Cicia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Amico","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Raucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ercolano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Maione","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Michela","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Ammendola","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II , Naples 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National Research Council , Pozzuoli ,","place":["Italy"]},{"name":"Epitech Group SpA , Saccolongo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Borrelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-5231","authenticated-orcid":false,"given":"Barbara","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo A","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II , Naples 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