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Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models
Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900005/ https://www.ncbi.nlm.nih.gov/pubmed/33633700 http://dx.doi.org/10.3389/fmicb.2021.570093 |
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author | Zhang, Song Zhang, Yingmiao Gan, Lu Wei, Fen Chai, Bao A Aljaafreh, Amaneh Abdel Hafez Liu, Xinxin Duan, Xiaoru Jiang, Jian Wang, Xin He, Mengwen Huang, Xian Cai, Huahua Chen, Tie Chen, Hongxiang |
author_facet | Zhang, Song Zhang, Yingmiao Gan, Lu Wei, Fen Chai, Bao A Aljaafreh, Amaneh Abdel Hafez Liu, Xinxin Duan, Xiaoru Jiang, Jian Wang, Xin He, Mengwen Huang, Xian Cai, Huahua Chen, Tie Chen, Hongxiang |
author_sort | Zhang, Song |
collection | PubMed |
description | Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women. |
format | Online Article Text |
id | pubmed-7900005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79000052021-02-24 Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models Zhang, Song Zhang, Yingmiao Gan, Lu Wei, Fen Chai, Bao A Aljaafreh, Amaneh Abdel Hafez Liu, Xinxin Duan, Xiaoru Jiang, Jian Wang, Xin He, Mengwen Huang, Xian Cai, Huahua Chen, Tie Chen, Hongxiang Front Microbiol Microbiology Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women. Frontiers Media S.A. 2021-02-09 /pmc/articles/PMC7900005/ /pubmed/33633700 http://dx.doi.org/10.3389/fmicb.2021.570093 Text en Copyright © 2021 Zhang, Zhang, Gan, Wei, Chai, A Aljaafreh, Liu, Duan, Jiang, Wang, He, Huang, Cai, Chen and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Zhang, Song Zhang, Yingmiao Gan, Lu Wei, Fen Chai, Bao A Aljaafreh, Amaneh Abdel Hafez Liu, Xinxin Duan, Xiaoru Jiang, Jian Wang, Xin He, Mengwen Huang, Xian Cai, Huahua Chen, Tie Chen, Hongxiang Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title | Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title_full | Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title_fullStr | Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title_full_unstemmed | Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title_short | Progesterone Suppresses Neisseria gonorrhoeae-Induced Inflammation Through Inhibition of NLRP3 Inflammasome Pathway in THP-1 Cells and Murine Models |
title_sort | progesterone suppresses neisseria gonorrhoeae-induced inflammation through inhibition of nlrp3 inflammasome pathway in thp-1 cells and murine models |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900005/ https://www.ncbi.nlm.nih.gov/pubmed/33633700 http://dx.doi.org/10.3389/fmicb.2021.570093 |
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