title: Global gene expression changes underlying Stachybotrys chartarum toxin-induced apoptosis in murine alveolar macrophages: evidence of multiple signal transduction pathways.
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.
authors.affiliation: Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Jagjit S
authors.initials: JS
authors.lastname: Yadav
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009183:Mycotoxins / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D018384:Oxidative Stress; D053218:Receptors, Death Domain / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013191:Stachybotrys / Q000235:genetics* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D009183:Mycotoxins; D016328:NF-kappa B; D053218:Receptors, Death Domain; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53; C038398:stachybotrotoxin; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases