Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients
BackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resist...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.923492/full |
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| author | Min Qiao Min Qiao Min Qiao Shanshan Li Jinfeng Yuan Weicong Ren Yuanyuan Shang Wei Wang Rongmei Liu Fuzhen Zhang Qing Li Xiao Wu Jie Lu Mengqiu Gao Yu Pang |
| author_facet | Min Qiao Min Qiao Min Qiao Shanshan Li Jinfeng Yuan Weicong Ren Yuanyuan Shang Wei Wang Rongmei Liu Fuzhen Zhang Qing Li Xiao Wu Jie Lu Mengqiu Gao Yu Pang |
| author_sort | Min Qiao |
| collection | DOAJ |
| description | BackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.ResultsA total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.ConclusionOur data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10. |
| first_indexed | 2024-04-13T21:18:44Z |
| format | Article |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T21:18:44Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-704332281479414cb645d7a82edab03e2022-12-22T02:29:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.923492923492Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patientsMin Qiao0Min Qiao1Min Qiao2Shanshan Li3Jinfeng Yuan4Weicong Ren5Yuanyuan Shang6Wei Wang7Rongmei Liu8Fuzhen Zhang9Qing Li10Xiao Wu11Jie Lu12Mengqiu Gao13Yu Pang14Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Gastroenterology, Shanxi Provincial People’s Hospital, Affiliate of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaBeijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaDepartment of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, ChinaBackgroundApart from bactericidal effects, anti-tuberculosis drugs can interfere with the host’s immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages.MethodsBased on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay.ResultsA total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs.ConclusionOur data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.https://www.frontiersin.org/articles/10.3389/fimmu.2022.923492/fulldelamanidCXCL10JAK/STAT1tuberculosisinflammation |
| spellingShingle | Min Qiao Min Qiao Min Qiao Shanshan Li Jinfeng Yuan Weicong Ren Yuanyuan Shang Wei Wang Rongmei Liu Fuzhen Zhang Qing Li Xiao Wu Jie Lu Mengqiu Gao Yu Pang Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients Frontiers in Immunology delamanid CXCL10 JAK/STAT1 tuberculosis inflammation |
| title | Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients |
| title_full | Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients |
| title_fullStr | Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients |
| title_full_unstemmed | Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients |
| title_short | Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients |
| title_sort | delamanid suppresses cxcl10 expression via regulation of jak stat1 signaling and correlates with reduced inflammation in tuberculosis patients |
| topic | delamanid CXCL10 JAK/STAT1 tuberculosis inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.923492/full |
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