{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:58:59Z","timestamp":1788785939591,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010402","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172885"],"award-info":[{"award-number":["32172885"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Fund of Heilongjiang Province for Excellent Young Scholars","award":["YQ2020C010"],"award-info":[{"award-number":["YQ2020C010"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p><jats:italic>Giardia duodenalis<\/jats:italic>, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. <jats:italic>Giardia<\/jats:italic> infection may persist over extended periods with intestinal inflammation, although minimal. Cyclooxygenase (COX)-2 is well known as an important inducer of inflammatory response, while the role it played in noninvasive <jats:italic>Giardia<\/jats:italic> infection remains elusive. Here we investigated the regulatory function of COX-2 in <jats:italic>Giardia<\/jats:italic>-induced pro-inflammatory response and defense-related nitric oxide (NO) generation in macrophage-like cell line, and identified the potential regulators. We initially found that <jats:italic>Giardia<\/jats:italic> challenge induced up-regulation of IL-1\u03b2, IL-6, TNF-\u03b1, prostaglandin (PG) E2, and COX-2 in macrophages, and pretreatment of the cells with COX-2 inhibitor NS398 reduced expressions of those pro-inflammatory factors. It was also observed that COX-2 inhibition could attenuate the up-regulated NO release and inducible NO synthase (iNOS) expression induced by <jats:italic>Giardia<\/jats:italic>. We further confirmed that <jats:italic>Giardia<\/jats:italic>-induced COX-2 up-regulation was mediated by the phosphorylation of p38 and ERK1\/2 MAPKs and NF-\u03baB. In addition, inhibition of reactive oxygen species (ROS) by NAC was shown to repress <jats:italic>Giardia<\/jats:italic>-induced activation of MAPK\/NF-\u03baB signaling, up-regulation of COX-2 and iNOS, increased levels of PGE2 and NO release, and up-expressions of IL-1\u03b2, IL-6, and TNF-\u03b1. Collectively, in this study, we revealed a critical role of COX-2 in modulating pro-inflammatory response and defense-related NO production in <jats:italic>Giardia<\/jats:italic>-macrophage interactions, and this process was evident to be controlled by ROS-dependent activation of MAPK\/NF-\u03baB signaling. The results can deepen our knowledge of anti-<jats:italic>Giardia<\/jats:italic> inflammatory response and host defense mechanisms.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010402","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T20:12:51Z","timestamp":1651176771000},"page":"e0010402","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":61,"title":["COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK\/NF-\u03baB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis"],"prefix":"10.1371","volume":"16","author":[{"given":"Yudan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuening","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiran","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-1864","authenticated-orcid":true,"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"pntd.0010402.ref001","doi-asserted-by":"crossref","first-page":"e0067221","DOI":"10.1128\/iai.00672-21","article-title":"The 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