Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1β and tissue damage, promoting its spread. Here, we established a...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/1805147 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832547601993433088 |
|---|---|
| author | Yan Fu Jingjing Shen Yinhong Li Fanglin Liu Bangzuo Ning Yuejuan Zheng Xin Jiang |
| author_facet | Yan Fu Jingjing Shen Yinhong Li Fanglin Liu Bangzuo Ning Yuejuan Zheng Xin Jiang |
| author_sort | Yan Fu |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1β and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug. |
| format | Article |
| id | doaj-art-caa51d5f5aae48569a78b0279f820324 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-caa51d5f5aae48569a78b0279f8203242025-02-03T06:44:02ZengWileyMediators of Inflammation1466-18612021-01-01202110.1155/2021/1805147Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosisYan Fu0Jingjing Shen1Yinhong Li2Fanglin Liu3Bangzuo Ning4Yuejuan Zheng5Xin Jiang6Center for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchCenter for Traditional Chinese Medicine and Immunology ResearchMycobacterium tuberculosis (Mtb) remains a significant threat to global health as it induces granuloma and systemic inflammatory responses during active tuberculosis. Mtb can induce macrophage pyroptosis, leading to the release of IL-1β and tissue damage, promoting its spread. Here, we established an in vitro Mtb-infected macrophage model to seek an effective antipyroptosis agent. Baicalin, isolated from Radix Scutellariae, was found to reduce pyroptosis in Mtb-infected macrophages. Baicalin could inhibit activation of the PERK/eIF2α pathway and thus downregulates TXNIP expression and subsequently reduces activation of the NLRP3 inflammasome, resulting in reduced pyroptosis in Mtb-infected macrophages. In conclusion, baicalin reduced pyroptosis by inhibiting the PERK/TXNIP/NLRP3 axis and might thus be a new adjuvant host-directed therapy (HDT) drug.http://dx.doi.org/10.1155/2021/1805147 |
| spellingShingle | Yan Fu Jingjing Shen Yinhong Li Fanglin Liu Bangzuo Ning Yuejuan Zheng Xin Jiang Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis Mediators of Inflammation |
| title | Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis |
| title_full | Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis |
| title_fullStr | Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis |
| title_full_unstemmed | Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis |
| title_short | Inhibition of the PERK/TXNIP/NLRP3 Axis by Baicalin Reduces NLRP3 Inflammasome-Mediated Pyroptosis in Macrophages Infected with Mycobacterium tuberculosis |
| title_sort | inhibition of the perk txnip nlrp3 axis by baicalin reduces nlrp3 inflammasome mediated pyroptosis in macrophages infected with mycobacterium tuberculosis |
| url | http://dx.doi.org/10.1155/2021/1805147 |
| work_keys_str_mv | AT yanfu inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT jingjingshen inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT yinhongli inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT fanglinliu inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT bangzuoning inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT yuejuanzheng inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis AT xinjiang inhibitionoftheperktxnipnlrp3axisbybaicalinreducesnlrp3inflammasomemediatedpyroptosisinmacrophagesinfectedwithmycobacteriumtuberculosis |