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Tumor necrosis factor and caspase in response to soluble or microparticle-incorporated drugs in Mycobacterium tuberculosis infection

Awadh Bihari Yadav¹ and Amit Misra¹

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1. Pharmaceutics Division, Central Drug Research Institute, Lucknow, India

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Document Type:

Poster

Date:

Received 28 September 2007 17:12 UTC; Posted 30 September 2007

Subjects:

Immunology, Pharmacology

Tags:

• Mycobacterium tuberculosis
• macrophages
• apoptosis

Abstract:

We 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 upregulated
We 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.

Presented at:

74th Annual meeting of Society of Biological Chemists (India), 07 December 2005

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This document is licensed to the public under the Creative Commons Attribution 2.5 License

How to cite this document:

Yadav, Awadh Bihari and Misra, Amit. Tumor necrosis factor and caspase in response to soluble or microparticle-incorporated drugs in Mycobacterium tuberculosis infection. Available from Nature Precedings <http://dx.doi.org/10.1038/npre.2007.1190.1> (2007)

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