Abstract
AbstractWe compared the effects of microparticles (MP) containig anti-tubercular drugs and those of the drugs themselves on the host macrophage (MΦ) response to infection with Mycobacterium tuberculosis H37Ra (Mtb). Mice infected intravenously with M. tb. were either administered rifampicin and isoniazid by oral gavage or through inhalation of biodegradable MP containing the two anti-tubercular drugs. Bronchoalveolar lavage (BAL) was perfomed to recover lung MΦ, which were cultured and the supernatant analysed for TNFα by ELISA. The murine MΦ cell line J774 or the human monocyte line THP-1 differentiated with phorbol myristate were infected in vitro and treated with MP or soluble drugs. The kinetics of secretion of TNFα were determined. Caspase-3 activity after infection and treatment was assesed using a substrate cleavage detection kit.MP, but not soluble drugs, strongly induced TNFα in infected cells. Uninfected cells also responded to MP, although less strongly. Caspase-3 was observed to be upregulatedWe conclude that MP treatment induces infected MΦ to upregulate the Th1 cytokine TNFα and Caspase-3, creating conditions for induction of apoptosis in these cells as a strategy to overcome infection.
Highlights
To test the hypothesis that microparticles (MP), with or without anti-tubercular drugs, activate a pro-apoptotic response in differentiated THP-1 cells infected with Mycobacterium tuberculosis (M.tb.); in the terms induction of early and late apoptosis, alteration of mitochondrial membrane potential, caspase-3, 8 & 9 activity, P2R activity
We examined the time kinetics of secretion of TNF-α and its role as a possible mediator of a pro-apoptotic response by infected Mφ to combat infection
We examined the induction of caspase-3, 8 & 9, alteration of MMP, P2R activity, induction of early apoptosis and late apoptosis
Summary
To test the hypothesis that microparticles (MP), with or without anti-tubercular drugs, activate a pro-apoptotic response in differentiated THP-1 cells infected with Mycobacterium tuberculosis (M.tb.); in the terms induction of early and late apoptosis, alteration of mitochondrial membrane potential, caspase-3, 8 & 9 activity, P2R activity
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