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Global gene expression changes underlying Stachybotrys chartarum toxin-induced apoptosis in murine alveolar macrophages: Evidence of multiple signal transduction pathways

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Abstract

The overall mechanism(s) underlying macrophage apoptosis caused by the toxins of the indoor mold Stachybotrys chartarum (SC) are not yet understood. In this direction, we report a microarray-based global gene expression profiling on the murine alveolar macrophage cell line (MH-S) treated with SC toxins for short (2 h) and long (24 h) periods, coinciding with the pre-apoptotic (<3 h) and progressed apoptotic stages of the treated cells, respectively. Microarray results on differential expression were validated by real-time RT-PCR analysis using representative gene targets. The toxin-regulated genes corresponded to multiple cellular processes, including cell growth, proliferation and death, inflammatory/immune response, genotoxic stress and oxidative stress, and to the underlying multiple signal transduction pathways involving MAPK-, NF-kB-, TNF-, and p53-mediated signaling. Transcription factor NF-kB showed dynamic temporal changes, characterized by an initial activation and a subsequent inhibition. Up-regulation of a battery of DNA damage-responsive and DNA repair genes in the early stage of the treatment suggested a possible role of genotoxic stress in the initiation of apoptosis. Simultaneous expression changes in both pro-survival genes and pro-apoptotic genes indicated the role of a critical balance between the two processes in SC toxin-induced apoptosis. Taken together, the results imply that multiple signaling pathways underlie the SC toxin-induced apoptosis in alveolar macrophages.

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Acknowledgments

The study was supported in part by the University of Cincinnati Research Incentive Award (JSY) and the University Graduate Scholarship Award (HW). We thank Dr. Mario Medvedovic of the Department of Environmental Health for the statistical help.

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  1. Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati Medical Center, Cincinnati, OH, 45267, USA

    Huiyan Wang & Jagjit S. Yadav

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  1. Huiyan Wang
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  2. Jagjit S. Yadav
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Correspondence to Jagjit S. Yadav.

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Wang, H., Yadav, J.S. Global gene expression changes underlying Stachybotrys chartarum toxin-induced apoptosis in murine alveolar macrophages: Evidence of multiple signal transduction pathways. Apoptosis 12, 535–548 (2007). https://doi.org/10.1007/s10495-006-0008-x

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