Cargando…

COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis

Giardia duodenalis, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. Giardia infection may persist over extended periods with intestinal inflammation, although minimal. Cyclooxygenase (COX)-2 is well known as an important induce...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Yudan, Yang, Yongwu, Liu, Min, Qin, Xuening, Yu, Xiran, Zhao, Huimin, Li, Xiaoyun, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089906/
https://www.ncbi.nlm.nih.gov/pubmed/35482821
http://dx.doi.org/10.1371/journal.pntd.0010402
_version_ 1784704616420605952
author Zhao, Yudan
Yang, Yongwu
Liu, Min
Qin, Xuening
Yu, Xiran
Zhao, Huimin
Li, Xiaoyun
Li, Wei
author_facet Zhao, Yudan
Yang, Yongwu
Liu, Min
Qin, Xuening
Yu, Xiran
Zhao, Huimin
Li, Xiaoyun
Li, Wei
author_sort Zhao, Yudan
collection PubMed
description Giardia duodenalis, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. Giardia 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 Giardia infection remains elusive. Here we investigated the regulatory function of COX-2 in Giardia-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 Giardia challenge induced up-regulation of IL-1β, IL-6, TNF-α, 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 Giardia. We further confirmed that Giardia-induced COX-2 up-regulation was mediated by the phosphorylation of p38 and ERK1/2 MAPKs and NF-κB. In addition, inhibition of reactive oxygen species (ROS) by NAC was shown to repress Giardia-induced activation of MAPK/NF-κB signaling, up-regulation of COX-2 and iNOS, increased levels of PGE2 and NO release, and up-expressions of IL-1β, IL-6, and TNF-α. Collectively, in this study, we revealed a critical role of COX-2 in modulating pro-inflammatory response and defense-related NO production in Giardia-macrophage interactions, and this process was evident to be controlled by ROS-dependent activation of MAPK/NF-κB signaling. The results can deepen our knowledge of anti-Giardia inflammatory response and host defense mechanisms.
format Online
Article
Text
id pubmed-9089906
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-90899062022-05-11 COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis Zhao, Yudan Yang, Yongwu Liu, Min Qin, Xuening Yu, Xiran Zhao, Huimin Li, Xiaoyun Li, Wei PLoS Negl Trop Dis Research Article Giardia duodenalis, the causative agent of giardiasis, is among the most important causes of waterborne diarrheal diseases around the world. Giardia 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 Giardia infection remains elusive. Here we investigated the regulatory function of COX-2 in Giardia-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 Giardia challenge induced up-regulation of IL-1β, IL-6, TNF-α, 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 Giardia. We further confirmed that Giardia-induced COX-2 up-regulation was mediated by the phosphorylation of p38 and ERK1/2 MAPKs and NF-κB. In addition, inhibition of reactive oxygen species (ROS) by NAC was shown to repress Giardia-induced activation of MAPK/NF-κB signaling, up-regulation of COX-2 and iNOS, increased levels of PGE2 and NO release, and up-expressions of IL-1β, IL-6, and TNF-α. Collectively, in this study, we revealed a critical role of COX-2 in modulating pro-inflammatory response and defense-related NO production in Giardia-macrophage interactions, and this process was evident to be controlled by ROS-dependent activation of MAPK/NF-κB signaling. The results can deepen our knowledge of anti-Giardia inflammatory response and host defense mechanisms. Public Library of Science 2022-04-28 /pmc/articles/PMC9089906/ /pubmed/35482821 http://dx.doi.org/10.1371/journal.pntd.0010402 Text en © 2022 Zhao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhao, Yudan
Yang, Yongwu
Liu, Min
Qin, Xuening
Yu, Xiran
Zhao, Huimin
Li, Xiaoyun
Li, Wei
COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title_full COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title_fullStr COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title_full_unstemmed COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title_short COX-2 is required to mediate crosstalk of ROS-dependent activation of MAPK/NF-κB signaling with pro-inflammatory response and defense-related NO enhancement during challenge of macrophage-like cell line with Giardia duodenalis
title_sort cox-2 is required to mediate crosstalk of ros-dependent activation of mapk/nf-κb signaling with pro-inflammatory response and defense-related no enhancement during challenge of macrophage-like cell line with giardia duodenalis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089906/
https://www.ncbi.nlm.nih.gov/pubmed/35482821
http://dx.doi.org/10.1371/journal.pntd.0010402
work_keys_str_mv AT zhaoyudan cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT yangyongwu cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT liumin cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT qinxuening cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT yuxiran cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT zhaohuimin cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT lixiaoyun cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis
AT liwei cox2isrequiredtomediatecrosstalkofrosdependentactivationofmapknfkbsignalingwithproinflammatoryresponseanddefenserelatednoenhancementduringchallengeofmacrophagelikecelllinewithgiardiaduodenalis