Mycobacterium tuberculosis Rv0426c promotes recombinant mycobacteria intracellular survival via manipulating host inflammatory cytokines and suppressing cell apoptosis

2020 ◽  
Vol 77 ◽  
pp. 104070 ◽  
Author(s):  
Cao Ruan ◽  
Jiang Li ◽  
Jingjing Niu ◽  
Ping Li ◽  
Yu Huang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Intracellular Survival

Celastrol Exerts Cardioprotective Effect in Rheumatoid Arthritis by Inhibiting TLR2/HMGB1 Signaling Pathway-Mediated Autophagy

2021 ◽  
pp. 1-10
Author(s):  
Xiaohong Lu ◽  
Sha Gong ◽  
Xiaojun Wang ◽  
Nan Hu ◽  
Dan Pu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Signal Pathway ◽  
Index Score ◽  
Cardioprotective Effect ◽  
Rat Cardiomyocytes ◽  
Swelling Degree ◽  
Collagen Iii

<b><i>Objective:</i></b> Rheumatoid arthritis (RA) is a kind of chronic inflammatory disease characterized by the release of inflammatory cytokines and cardiomyocyte apoptosis, which lead to increased riskfor heart diseases. This study aims to explore the possible effect and mechanism of Celastrol on RA induced cardiac impairments in rats. <b><i>Methods:</i></b> Collagen induced RA wistar rat models (CIA) were established for the measurement on secondary foot swelling degree, polyarthritis index score, spleen and thymus index. Pathological morphology was observed using H&amp;E staining. Heart fibrosis was measured after Sirius red staining, while cell apoptosis was determined by TUNEL staining. For in vitro experiments, rat cardiomyocytes were isolated to determine the inflammatory cytokine secretion and cell apoptosis using ELISA and flow cytometry, respectively. Protein expressions of related index and autophagy were detected by Western blot and immunofluorescence. <b><i>Results:</i></b> CIA rat model was successfully established and characterized by severe secondary foot swelling degree, and increased polyarthritis index score and spleen and thymus index. Synovial hyperplasia, disordered cardiomyocytes, cell infiltration and fibrosis were also observed in CIA rat model. Compared with CIA model, Celastrol treatment could suppress the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β, as well as inhibiting the expressions of Bax, cleaved caspase3, collagen I, collagen III and α-SMA. In addition to that, Celastrol treatment can attenuate cell apoptosis and fibrosis of cardiomyocytes and elevate Bcl-2 expression. RA induced cell autophagy can be suppressed by Celastrol through inhibiting the activation of TLR2/HMGB1 signal pathway. <b><i>Conclusion:</i></b> Celastrol can regulate TLR2/HMGB1 signal pathway to suppress autophagy and therefore exert cardioprotective effect in RA.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

scholarly journals Inhibition of Ca2+ Signaling by Mycobacterium tuberculosisIs Associated with Reduced Phagosome–Lysosome Fusion and Increased Survival within Human Macrophages

2000 ◽  
Vol 191 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Zulfiqar A. Malik ◽  
Gerene M. Denning ◽  
David J. Kusner
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Macrophage Activation ◽  
Fold Increase ◽  
Intracellular Survival ◽  
Complement Receptor ◽  
Ionophore A23187 ◽  
Protein Markers ◽  
Human Macrophages ◽  
Lysosomal Protein

Complement receptor (CR)-mediated phagocytosis of Mycobacterium tuberculosis by macrophages results in intracellular survival, suggesting that M. tuberculosis interferes with macrophage microbicidal mechanisms. As increases in cytosolic Ca2+ concentration ([Ca2+]c) promote phagocyte antimicrobial responses, we hypothesized that CR phagocytosis of M. tuberculosis is accompanied by altered Ca2+ signaling. Whereas the control complement (C)-opsonized particle zymosan (COZ) induced a 4.6-fold increase in [Ca2+]c in human macrophages, no change in [Ca2+]c occurred upon addition of live, C-opsonized virulent M. tuberculosis. Viability of M. tuberculosis and ingestion via CRs was required for infection of macrophages in the absence of increased [Ca2+]c, as killed M. tuberculosis or antibody (Ab)-opsonized, live M. tuberculosis induced elevations in [Ca2+]c similar to COZ. Increased [Ca2+]c induced by Ab-opsonized bacilli was associated with a 76% reduction in intracellular survival, compared with C-opsonized M. tuberculosis. Similarly, reversible elevation of macrophage [Ca2+]c with the ionophore A23187 reduced intracellular viability by 50%. Ionophore-mediated elevation of [Ca2+]c promoted the maturation of phagosomes containing live C-opsonized bacilli, as evidenced by acidification and accumulation of lysosomal protein markers. These data demonstrate that M. tuberculosis inhibits CR-mediated Ca2+ signaling and indicate that this alteration of macrophage activation contributes to inhibition of phagosome–lysosome fusion and promotion of intracellular mycobacterial survival.

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