MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/2432904 |
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| author | Qingwen Zhang Xinru Jiang Weigang He Kailin Wei Jinxia Sun Xiangyang Qin Yuejuan Zheng Xin Jiang |
| author_facet | Qingwen Zhang Xinru Jiang Weigang He Kailin Wei Jinxia Sun Xiangyang Qin Yuejuan Zheng Xin Jiang |
| author_sort | Qingwen Zhang |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264.7 by downregulating the activation of nuclear factor kappa B (NF-κB) and NLRP3 inflammasome. Evidences showed that MCL decreased the secretion of Mtb-induced inflammatory cytokines (IL-1β and TNF-α) in a dose-dependent manner. Meanwhile, MCL dramatically suppressed Mtb-induced activation of iNOS and COX2 as well as subsequent production of NO. Furthermore, MCL inhibited Mtb-induced phosphorylation of Akt (Ser 473) in Raw264.7. According to our results, MCL plays an important role in modulating Mtb-induced inflammatory response through PI3K/Akt/NF-κB pathway and subsequently downregulating the activation of NLRP3 inflammasome. Therefore, MCL may represent as a potential drug candidate in the adjuvant treatment of TB by regulating host immune response. |
| format | Article |
| id | doaj-art-16f53f84fde24a9986646a713ede5c82 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-16f53f84fde24a9986646a713ede5c822025-02-03T01:10:22ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/24329042432904MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome ActivationQingwen Zhang0Xinru Jiang1Weigang He2Kailin Wei3Jinxia Sun4Xiangyang Qin5Yuejuan Zheng6Xin Jiang7Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaDepartment of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaDepartment of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaMajor in Biology, The University of British Columbia, Vancouver, V6T 1Z4, CanadaDepartment of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaDepartment of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaanxi 710034, ChinaDepartment of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaDepartment of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, ChinaMycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264.7 by downregulating the activation of nuclear factor kappa B (NF-κB) and NLRP3 inflammasome. Evidences showed that MCL decreased the secretion of Mtb-induced inflammatory cytokines (IL-1β and TNF-α) in a dose-dependent manner. Meanwhile, MCL dramatically suppressed Mtb-induced activation of iNOS and COX2 as well as subsequent production of NO. Furthermore, MCL inhibited Mtb-induced phosphorylation of Akt (Ser 473) in Raw264.7. According to our results, MCL plays an important role in modulating Mtb-induced inflammatory response through PI3K/Akt/NF-κB pathway and subsequently downregulating the activation of NLRP3 inflammasome. Therefore, MCL may represent as a potential drug candidate in the adjuvant treatment of TB by regulating host immune response.http://dx.doi.org/10.1155/2017/2432904 |
| spellingShingle | Qingwen Zhang Xinru Jiang Weigang He Kailin Wei Jinxia Sun Xiangyang Qin Yuejuan Zheng Xin Jiang MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation Mediators of Inflammation |
| title | MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation |
| title_full | MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation |
| title_fullStr | MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation |
| title_full_unstemmed | MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation |
| title_short | MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation |
| title_sort | mcl plays an anti inflammatory role in mycobacterium tuberculosis induced immune response by inhibiting nf κb and nlrp3 inflammasome activation |
| url | http://dx.doi.org/10.1155/2017/2432904 |
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