scholarly journals The role of Mycobacterium tuberculosis complex species on apoptosis and necroptosis state of macrophages derived from active pulmonary tuberculosis patients

2020 ◽  
Author(s):  
Budi Yanti ◽  
Mulyadi Mulyadi ◽  
Muhammad Amin ◽  
Harapan Harapan ◽  
Ni Made Mertaniasih ◽  
...  

Abstract Objective: The role of Mycobacterium tuberculosis complex (MTBC) species in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether M. tuberculosis and M. bovis is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), and the level of apoptosis.Results: We recruited 30 patients of pulmonary TB; 24 patients were infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. M. tuberculosis-infected patients were more likely to have severe lung damage compared to those infected with M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was associated with lower expression of FADD and lower apoptosis level of macrophages compared to M. bovis. No significant different of RIP3 between MTBC species groups. In conclusion, M. tuberculosis Beijing strain was associated with severe pulmonary damage, inhibited FADD expression and reduced apoptosis level of macrophages derived from TB. This suggests that the M. tuberculosis Beijing strain is potentially to be used as determinant of disease progressivity and tissue damage in TB cases.

2020 ◽  
Author(s):  
Budi Yanti ◽  
Mulyadi Mulyadi ◽  
Muhammad Amin ◽  
Harapan Harapan ◽  
Ni Made Mertaniasih ◽  
...  

Abstract Objective: The role of Mycobacterium tuberculosis complex (MTBC) species in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether M. tuberculosis and M. bovis is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), and the level of apoptosis. Results: We recruited 30 patients with pulmonary TB; 24 patients were infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. M. tuberculosis-infected patients were more likely to have severe lung damage compared to those infected with M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was associated with lower expression of FADD and lower apoptosis level of macrophages compared to M. bovis. No significant different of RIP3 between MTBC species groups. In conclusion, M. tuberculosis Beijing strain was associated with severe pulmonary damage, inhibited FADD expression and reduced apoptosis level of macrophages derived from pulmonary TB patients. This suggests that the M. tuberculosis Beijing strain is potentially to be used as determinant of disease progressivity and tissue damage in TB cases.


2020 ◽  
Author(s):  
Budi Yanti ◽  
Mulyadi Mulyadi ◽  
Muhammad Amin ◽  
Harapan Harapan ◽  
Ni Made Mertaniasih ◽  
...  

Abstract Objective The role of Mycobacterium tuberculosis complex (MTBC) strain in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether MTBC strain is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), as well as the level of apoptosis. Results We recruited 24 TB patients infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. Data indicated that those who infected with M. tuberculosis were more frequent to have severe lung damage than M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was also associated with lower expression of FADD and lower apoptosis level of macrophage cells compared to M. bovis . No significant different of RIP3 between strain groups. In conclusion, M. tuberculosis Beijing strain is associated with severe pulmonary damage, inhibits FADD expression and reduces apoptosis level in macrophages derived from TB. This suggests that MTBC strain potentially be used as determinant of progressivity of disease and tissue damage in TB cases.


2020 ◽  
Author(s):  
Budi Yanti ◽  
Mulyadi Mulyadi ◽  
Muhammad Amin ◽  
Harapan Harapan ◽  
Ni Made Mertaniasih ◽  
...  

Abstract Objective The role of Mycobacterium tuberculosis complex (MTBC) strain in tuberculosis (TB) infection in human is still questioned. The aim of this study was to determine whether MTBC strain is associated with apoptosis and necroptosis by measuring the expression of specific signaling pathways components (Fas-associated protein with death domain (FADD) and receptor interacting protein 3 (RIP3)), as well as the level of apoptosis.Results We recruited 24 TB patients infected with M. tuberculosis Beijing strain and six patients with M. bovis BCG strain. Data indicated that those who infected with M. tuberculosis were more frequent to have severe lung damage than M. bovis (odds ratio [OR]: 7.60; 95% confidence interval [CI]: 1.07-54.09). M. tuberculosis infection was also associated with lower expression of FADD and lower apoptosis level of macrophage cells compared to M. bovis . No significant different of RIP3 between strain groups. In conclusion, M. tuberculosis Beijing strain is associated with severe pulmonary damage, inhibits FADD expression and reduces apoptosis level in macrophages derived from TB. This suggests that MTBC strain potentially be used as determinant of progressivity of disease and tissue damage in TB cases.


2004 ◽  
Vol 287 (3) ◽  
pp. C633-C642 ◽  
Author(s):  
Laurie E. Kilpatrick ◽  
Shuang Sun ◽  
Helen M. Korchak

TNF is implicated in the attenuation of neutrophil constitutive apoptosis during sepsis. Antiapoptotic signaling is mediated principally through the TNF receptor-1 (TNFR-1). In adherent neutrophils, when β-integrin signaling is activated, TNF phosphorylates TNFR-1 and activates prosurvival and antiapoptotic signaling. Previously, we identified the δ-PKC isotype and phosphatidylinositol (PI) 3-kinase as critical regulators of TNF signaling in adherent neutrophils. Both kinases associate with TNFR-1 in response to TNF and are required for TNFR-1 serine phosphorylation, NF-κB activation, and inhibition of apoptosis. The purpose of this study was to examine the role of δ-PKC and PI 3-kinase in the assembly of TNFR-1 signaling complex that regulates NF-κB activation and antiapoptotic signaling. Coimmunoprecipitation studies established that PI 3-kinase, δ-PKC, and TNFR-1 formed a signal complex in response to TNF. δ-PKC recruitment required both δ-PKC and PI 3-kinase activity, whereas PI 3-kinase recruitment was δ-PKC independent, suggesting that PI 3-kinase acts upstream of δ-PKC. An important regulatory step in control of antiapoptotic signaling is the assembly of the TNFR-1-TNFR-1-associated death domain protein (TRADD)-TNFR-associated factor 2 (TRAF2)-receptor interacting protein (RIP) complex that controls NF-κB activation. Inhibition of either δ-PKC or PI 3-kinase decreased TNF-mediated recruitment of RIP and TRAF2 to TNFR-1. In contrast, TRADD recruitment was enhanced. Thus δ-PKC and PI 3-kinase are positive regulators of TNF-mediated association of TRAF2 and RIP with TNFR-1. Conversely, these kinases are negative regulators of TRADD association. These results suggest that δ-PKC and PI 3-kinase regulate TNF antiapoptotic signaling at the level of the TNFR-1 through control of assembly of a TNFR-1-TRADD-RIP-TRAF2 complex.


2018 ◽  
Vol 18 (7) ◽  
pp. 1054-1063 ◽  
Author(s):  
Ning Ding ◽  
Hong Zhang ◽  
Shan Su ◽  
Yumei Ding ◽  
Xiaohui Yu ◽  
...  

Background: Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective: Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method: CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results: Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drugresistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion: This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes.


2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.


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