Modulation of IL-10 and TNF-alpha Expression Following Hippocampal Apoaequorin Administration
Mentor 1
James R. Moyer, Jr.
Location
Union Wisconsin Room
Start Date
24-4-2015 10:30 AM
End Date
24-4-2015 11:45 AM
Description
Stroke is one of the leading causes of death in the United States and is responsible for a fatality every four minutes (Go et al., 2013). During stroke, excessive calcium floods into neurons and is released from intracellular stores, leading to excitotoxicity and activation of molecules that signal cell death. Upregulation of calcium binding proteins (CaBPs) can buffer excess intracellular calcium and reduce cell death (Fan et al., 2007). Previous studies in our lab have shown that local infusion of the CaBP apoaequorin (AQ) reduces cell death within the hippocampus in an in vitro model of ischemia (Detert et al., 2013). Infusion of AQ also results in concurrent modulation of cytokine and chemokine mRNA, indicating a neuroimmunomodulatory response. In particular, IL-10 mRNA is significantly elevated at 1 h after AQ infusion and remains upregulated for at least 48 hrs following AQ infusion. Additionally, TNF-alpha mRNA is significantly upregulated at 1 h, but downregulated by 48 hr post-infusion (Detert et al., 2013). Here we investigate the translation of these mRNAs into proteins during the same time course. In the current study, animals were unilaterally infused into the dorsal hippocampus with 4% AQ at 1 h, 1 d, or 2 d prior to tissue collection. Contralateral vehicle injection served as control. We demonstrate that IL-10 protein expression parallels mRNA expression; upregulated at 1 h post-infusion, decreasing thereafter. On the other hand, TNF-alpha protein expression does not change at 1 h, and is significantly downregulated at 2 d as compared to 1 d post-infusion. These data suggest that one possible mechanism by which AQ may protect neurons may involve a neuroimmunomodulatory response involving an upregulation of IL-10 and a downregulation of TNF-alpha.
Modulation of IL-10 and TNF-alpha Expression Following Hippocampal Apoaequorin Administration
Union Wisconsin Room
Stroke is one of the leading causes of death in the United States and is responsible for a fatality every four minutes (Go et al., 2013). During stroke, excessive calcium floods into neurons and is released from intracellular stores, leading to excitotoxicity and activation of molecules that signal cell death. Upregulation of calcium binding proteins (CaBPs) can buffer excess intracellular calcium and reduce cell death (Fan et al., 2007). Previous studies in our lab have shown that local infusion of the CaBP apoaequorin (AQ) reduces cell death within the hippocampus in an in vitro model of ischemia (Detert et al., 2013). Infusion of AQ also results in concurrent modulation of cytokine and chemokine mRNA, indicating a neuroimmunomodulatory response. In particular, IL-10 mRNA is significantly elevated at 1 h after AQ infusion and remains upregulated for at least 48 hrs following AQ infusion. Additionally, TNF-alpha mRNA is significantly upregulated at 1 h, but downregulated by 48 hr post-infusion (Detert et al., 2013). Here we investigate the translation of these mRNAs into proteins during the same time course. In the current study, animals were unilaterally infused into the dorsal hippocampus with 4% AQ at 1 h, 1 d, or 2 d prior to tissue collection. Contralateral vehicle injection served as control. We demonstrate that IL-10 protein expression parallels mRNA expression; upregulated at 1 h post-infusion, decreasing thereafter. On the other hand, TNF-alpha protein expression does not change at 1 h, and is significantly downregulated at 2 d as compared to 1 d post-infusion. These data suggest that one possible mechanism by which AQ may protect neurons may involve a neuroimmunomodulatory response involving an upregulation of IL-10 and a downregulation of TNF-alpha.
