Isoniazid Induces Apoptosis Of Activated CD4+ T Cells

Tousif, Sultan; Singh, Dhiraj Kumar; Ahmad, Shaheer; Moodley, Prashini; Bhattacharyya, Maitree; Kaer, Luc Van; Das, Gobardhan

doi:10.1074/jbc.c114.598946

Cited by 51 publications

(39 citation statements)

References 29 publications

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“…Tousif et al. [47] found that INH may decrease the function of CD4 T-cells via inducing apoptosis. These other potential vitamin D regulated pathways were worthy of further exploration.…”

Section: Discussionmentioning

confidence: 99%

The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages

Chesdachai

Zughaier

et al. 2016

Journal of Clinical & Translational Endocrinology

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Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages. To address this hypothesis, human macrophage-like monocytic (THP-1) cells were treated with varying doses of first-line anti-tuberculosis drugs in the presence of the active form of vitamin D, 1N1,25-dihydroxyvitamin D3 (1,25(OH)2D3). The expression of hCAP18 was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 1,25(OH)2D3 strongly induced expression of hCAP18 mRNA in THP-1 cells (fold-change from control). The combination of the standard 4-drug TB therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) in the cultured THP-1 cells demonstrated a significant decrease of hCAP18 mRNA at the dosage of 10 ug/mL. In 31 subjects with newly diagnosed drug-sensitive TB randomized to either high-dose vitamin D3 (1.2 million IU over 8 weeks, n=13) versus placebo (n=18), there was no change from baseline to week 8 in hCAP18 mRNA levels in peripheral blood mononuclear cells or in plasma concentrations of LL-37, the protein product of hCAP18.These data suggest that first-line anti-TB drugs may alter the vitamin D-dependent increase in hCAP18 and LL-37 human macrophages.

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“…Tousif et al. [47] found that INH may decrease the function of CD4 T-cells via inducing apoptosis. These other potential vitamin D regulated pathways were worthy of further exploration.…”

Section: Discussionmentioning

confidence: 99%

The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages

Chesdachai

Zughaier

et al. 2016

Journal of Clinical & Translational Endocrinology

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“…We followed the protocol for surface and intracellular staining for flow cytometry as described earlier by Tousif et al (22). …”

Section: Methodsmentioning

confidence: 99%

Nanoparticle-Formulated Curcumin Prevents Posttherapeutic Disease Reactivation and Reinfection with Mycobacterium tuberculosis following Isoniazid Therapy

et al. 2017

Self Cite

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Curcumin, the bioactive component of turmeric also known as “Indian Yellow Gold,” exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. Even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. Therefore, the translational potential of this compound is specifically challenged by bioavailability issues, and several laboratories are making efforts to improve its bioavailability. We developed a simple one-step process to generate curcumin nanoparticles of ~200 nm in size, which yielded a fivefold enhanced bioavailability in mice over regular curcumin. Curcumin nanoparticles drastically reduced hepatotoxicity induced by antitubercular antibiotics during treatment in mice. Most interestingly, co-treatment of nanoparticle-formulated curcumin along with antitubercular antibiotics dramatically reduced the risk for disease reactivation and reinfection, which is the major shortfall of current antibiotic treatment adopted by Directly Observed Treatment Short-course. Furthermore, nanoparticle-formulated curcumin significantly reduced the time needed for antibiotic therapy to obtain sterile immunity, thereby reducing the possibility of generating drug-resistant variants of the organisms. Therefore, adjunct therapy of nano-formulated curcumin with enhanced bioavailability may be beneficial to treatment of tuberculosis and possibly other diseases.

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“…1C ). Recently, Tousif et al showed that the anti-TB drug INH strongly induces apoptosis of activated CD4 + T cells and reduces Mtb antigen-specific immune responses[28], suggesting that anti-TB drugs induce host cell damage as well as mycobacterial killing. In contrast to most commonly used anti-TB drugs, pasakbumin A was sufficient to protect Mtb-infected Raw264.7 cells compared to cells infected with Mtb alone, and it did not exhibit any cytotoxic effects in macrophages ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages

Lee

Kim

et al. 2018

Preprint

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17 Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis 18(Mtb) and remains a major health problem worldwide. Thus, there is an urgent need to identify 19 new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to 20 reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes. 21In this study, to develop a novel candidate drug for effective TB treatment with few side effects 22 in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E. longifolia) Jack,

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Isoniazid Induces Apoptosis Of Activated CD4+ T Cells

Cited by 51 publications

References 29 publications

The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages

The effects of first-line anti-tuberculosis drugs on the actions of vitamin D in human macrophages

Nanoparticle-Formulated Curcumin Prevents Posttherapeutic Disease Reactivation and Reinfection with Mycobacterium tuberculosis following Isoniazid Therapy

Pasakbumin A controls the growth of Mycobacterium tuberculosis by enhancing the autophagy and production of antibacterial mediators in mouse macrophages

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