Faculty
James J. Pestka, Professor
Ph.D., Cornell University, 1979
B.S., State University College at Buffalo, 1975
234A G.M. Trout FSHN Building
Michigan State University
East Lansing, MI 48824-1224
Phone: (517) 355-8474, Ext. 125
Lab: (517) 355-8474, Ext. 171
Fax: (517) 353-8963
E-mail: pestka@msu.edu
Research Interests:
Molecular mechanisms of trichothecene toxicity
Trichothecenes are a novel class of natural toxins produced by fungi in food and the environment that can both induce and suppress inflammatory gene expression thereby disrupting immune function. These compounds bind to eukaryotic ribosomes and initiate a stress response involving activation of protein kinases. We are studying the molecular linkages between the ribosome and these stress-related kinases as well as their relation to downstream gene regulation and apoptosis. These studies will have relevance to other ribotoxic agents such as ricin and shiga toxin.
Dietary modulation of viral-induced mucosal immune responses
Reoviruses induce a robust self-limiting immune response in both the gut and respiratory tract that involve humoral and cell-mediated arms of the immune system. We are using reovirus as a model to study mechanisms by which trichothecene mycotoxins and dietary factors alter mucosal immune function and thereby impact viral clearance and shedding. Data from these studies will provide insight into the role of diet in increasing or decreasing resistance to viral infection.
Omega-3 fatty acid suppression of experiemental IgA nephropathy (IgAN)
Consumption of the trichothecene deoxynivalenol aberrantly induces upregulation of IgA production in the mouse that mimics human IgAN, the most type of glomerulonephritis worldwide. Dietary supplementation with omega-3 fatty acids found in fish oil has been shown to have benefits to patients with this disease but the mechanism is unknown. We are studying how omega-3s suppress protein kinase activation and downstream inflammatory cytokines expression involved in our IgAN model other models of inflammation. The results will have broad implications for use of these supplements by an estimated 26 million U.S. adults — largely for prevention of inflammation
Upper respiratory tract targets of black mold trichothecenes:
The black mold Stachybotrys chartarum frequently occurs in water-damaged buildings and has been associated with illnesses associated with respiratory tract inflammation, immune dysfunction and neurocognitive problems. We have determined that, at very low concentrations, macrocylic trichothecenes produced by this mold can induce both program cell death in olfactory sensory neurons and a robust inflammatory response in the mouse nasal compartment. We are studying mechanistic basis for these effects and relating this to dose, chronic exposure and interaction with airborne inflammagens such as endotoxin. These studies will impact risk assessment and management strategies of this environmental agent.
Instructional Activities:
FSC 440 – Food Microbiology
Recent Publications:
Islam Z, Amuzie CJ, Harkema J R, and Pestka J J 2007. "Neurotoxicity and inflammation in the nasal airways of mice exposed to the macrocyclic trichothecene mycotoxin roridin A: kinetics and potentiation by bacterial lipopolysaccharide co-exposure." Toxicol. Sci.
Li M, Harkema J R, Cuff C F, and Pestka J J. 2007. "Deoxynivalenol exacerbates viral bronchopneumonia induced by respiratory reovirus infection." Toxicol. Sci. 95:412-426.
Li M, Harkema J R, Islam Z, Cuff CF, and Pestka JJ. 2006. "T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates viral bronchiolitis." Toxicol. Appl. Pharmacol. 217:76-85.
Pestka J, and Zhou HR. 2006. "Toll-like receptor priming sensitizes macrophages to proinflammatory cytokine gene induction by deoxynivalenol and other toxicants." Toxicol. Sci. 92:445-455.
Mbandi E, and Pestka JJ. 2006. "Deoxynivalenol and satratoxin g potentiate proinflammatory cytokine and MIP-2 induction by Listeria and Salmonella in the macrophage." J. Food Prot. 69:1334-1339.
Shi Y, and Pestka JJ. "Attenuation of mycotoxin-induced IgA nephropathy by eicosapentaenoic acid in the mouse: dose response and relation to IL-6 expression." J. Nutr. Biochem. Jan. 9, 2006.
Li M, Cuff CF and Pestka JJ. "T-2 toxin impairment of enteric reovirus clearance in the mouse associated with suppressed immunoglobulin and IFN-gamma responses." Toxicol. Appl. Pharmacol. Feb. 24, 2006.
Jia Q, Zhou HR, Shi Y and Pestka JJ. "Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages." J. Nutr. 136(2):366-72, 2006.
Islam Z, Gray JS and Pestka JJ. "P38 mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes." Toxicol. Appl. Pharmacol. Dec. 15, 2005.
Islam Z and Pestka JJ. "LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse." Toxicol. Appl. Pharmacol. 211(1):53-63, 2006.
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