{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:59:57Z","timestamp":1791910797333,"version":"4.3.4"},"reference-count":60,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["2020R1A6C101A191"],"award-info":[{"award-number":["2020R1A6C101A191"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A1A03015642"],"award-info":[{"award-number":["2017R1A6A1A03015642"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Senile pruritus is a specific type of itching that occurs in elderly persons. Previously, we assessed antagonism of the nonselective ligand-gated cation channel transient receptor potential vanilloid 1 (TRPV1; capsaicin receptor or vanilloid receptor 1) and attenuation of atopic dermatitis by the non-steroidal TRPV1 antagonist PAC-14028 in clinical studies. The findings led us to postulate that PAC-14028 may also reduce itching in elderly people by antagonizing the TRPV1 pathway. In this study, we evaluated whether PAC-14028 modulates inflammatory markers present in senile pruritus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>HaCaT, RAW264.7, and differentiated THP-1 cells under itching-inducing conditions were treated with zymosan or IL-17A and variety of experimental approaches such as molecular modeling simulations, site-directed mutagenesis, overexpression strategies, confocal microscopy, mRNA analyses, and immunoprecipitation\/Western blotting analyses were assessed to check changes in inflammatory markers and explore the underlying mechanisms of PAC-14028 activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In the bioinformatic analyses, skin inflammation markers were found to be closely related to TRPV1, and the MAPK and NF-\u03baB pathways were upregulated when TRPV1 was activated. In HaCaT cells, PAC-14028 was found to directly bind to TRPV1, inhibiting inflammatory cytokine gene expression and downstream MAPK and NF-\u03baB signaling under various skin inflammatory conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>By combining the results of multiple assays, we were able to elucidate the molecular mechanism of PAC-14028 to TRPV1. Taken together, the findings indicate that PAC-14028 as a potential therapeutic agent for elderly people with pruritus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03946320251321354","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T02:39:57Z","timestamp":1741747197000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Attenuation of senile pruritus by PAC-14028-mediated downregulation of the NF-\u03baB and MAPK pathways"],"prefix":"10.1177","volume":"39","author":[{"given":"Ji Hye","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Biocosmetics, Sungkyunkwan University, Suwon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung Young","family":"Woo","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific, Yongin, Republic of Korea"},{"name":"Department of Applied Chemistry &amp; Biological Engineering, Ajou University, Suwon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Systems Biomedical Science, Soongsil University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":false,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biocosmetics, Sungkyunkwan University, Suwon, Republic of Korea"},{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2005.02607.x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp588"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(18)30044-5"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.139.11.1463"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212521"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1997.00440260028006"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.5152\/eurjrheum.2017.17037"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.07.013"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2019.08.438"},{"key":"e_1_3_4_11_2","first-page":"1146","article-title":"Endothelin-1 causes pruritus in mice","volume":"231","author":"Trentin PG","year":"2006","unstructured":"Trentin PG, Fernandes MB, D\u2019Orl\u00e9ans-Juste P, et al (2006) Endothelin-1 causes pruritus in mice. Experimental Biology and Medicine 231: 1146\u20131151.","journal-title":"Experimental Biology and Medicine"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2015.07.002"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9041190"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.016"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.06.002"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.5070\/D32611048118"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01857-2"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000524"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/15680266112129990090"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1037925"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116135"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142819"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136379"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.487"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6997(25)06664-5"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0454-04.2004"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.111534"},{"key":"e_1_3_4_29_2","first-page":"8","article-title":"TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery","volume":"62","author":"Yun J-W","year":"2011","unstructured":"Yun J-W, Seo JA, Jeong YS, et al (2011) TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. Journal of Dermatological Science 62: 8\u201315.","journal-title":"Journal of Dermatological Science"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-012-0321-6"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17455"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2020.104613"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17455"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.09.024"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.01.001"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2022.10.003"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.07.001"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2023.10.001"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2022.04.003"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.08.001"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117574"},{"key":"e_1_3_4_42_2","article-title":"Anti-inflammatory, antioxidative, and moisturizing effects of Oxyceros Horridus Lour. Ethanol extract in human keratinocytes via the p38 signaling pathway","volume":"21","author":"Sutopo NC","year":"2024","unstructured":"Sutopo NC, Rahmawati L, Huang L, et al (2024) Anti-inflammatory, antioxidative, and moisturizing effects of Oxyceros Horridus Lour. Ethanol extract in human keratinocytes via the p38 signaling pathway. Chemistry & Biodiversity 21: e202301791.","journal-title":"Chemistry & Biodiversity"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155167"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2024.07.002"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010018"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-021-00616-3"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-023-03983-z"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00908-X"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154824"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3646"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01087"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241713521"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1162"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-1811(02)00064-6"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-022-01250-6"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.009"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1177\/0960327121991911"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14464"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12786"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0906-6705.2004.0178.x"},{"key":"e_1_3_4_61_2","first-page":"279","article-title":"Assessing the synergistic effect of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis","volume":"18","author":"Kircik LH","year":"2019","unstructured":"Kircik LH, Papp KA, Stein Gold L, et al (2019) Assessing the synergistic effect of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in moderate-to-severe plaque psoriasis. Journal of Drugs in Dermatology 18: 279\u2013284.","journal-title":"Journal of Drugs in Dermatology"}],"container-title":["International Journal of Immunopathology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03946320251321354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03946320251321354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03946320251321354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:01:04Z","timestamp":1777456864000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03946320251321354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":60,"alternative-id":["10.1177\/03946320251321354"],"URL":"https:\/\/doi.org\/10.1177\/03946320251321354","relation":{},"ISSN":["0394-6320","2058-7384"],"issn-type":[{"value":"0394-6320","type":"print"},{"value":"2058-7384","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"article-number":"03946320251321354"}}