Abstract
Microglia are the resident macrophages in the central nervous system (CNS) and play essential roles in neuronal homeostasis and neuroinflammatory pathologies. Recently, microglia have been shown to contribute decisively to neuropathologic processes after ischemic stroke. Furthermore, natural compounds have been reported to attenuate inflammation and pathologies associated with neuroinflammation. Tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) is a phytoalkaloid with known anti-inflammatory effects in cells. In present study, the authors confirmed middle cerebral artery occlusion (MCAO) injury triggers the activation of microglia in brain tissue, and investigated whether tryptanthrin influences the function of mouse murine BV2 microglia under LPS-induced inflammatory conditions in vitro. It was found tryptanthrin protected BV2 microglia cells against LPS-induced inflammation and inhibited the induction of M1 phenotype microglia under inflammatory conditions. In addition, tryptanthrin reduced the production of pro-inflammatory cytokines in BV2 microglia cells via nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling and NF-κB signaling. The authors suggest that tryptanthrin might alleviate the progress of neuropathologies by controlling microglial functions under neuroinflammatory conditions.
Highlights
Microglia are a type of mononuclear macrophage (Butovsky et al, 2012; Prinz and Priller, 2014) and are the main macrophages involved in inflammatory response in the central nervous system (CNS; Graeber and Streit, 2010), and reportedly, are important regulators of homeostasis and neuroinflammation (Cianciulli et al, 2016)
To examine microglia activation in mouse brain tissues, we checked the expression of CD68 (Song and Lee, 2015) by immunostaining (Figure 1A)
Our results showed that the protein levels of iNOS and COX-2 were markedly increased in LPS treated BV2 microglia cells, and that tryptanthrin pretreatment inhibited these increases (Figure 2C)
Summary
Microglia are a type of mononuclear macrophage (Butovsky et al, 2012; Prinz and Priller, 2014) and are the main macrophages involved in inflammatory response in the central nervous system (CNS; Graeber and Streit, 2010), and reportedly, are important regulators of homeostasis and neuroinflammation (Cianciulli et al, 2016) Under stressful conditions, such as, in the presence of infection or inflammation, microglia are activated (Graeber and Streit, 2010), and secrete a variety of inflammatory mediators, such as, tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-10, and mediators of inflammation, such as, reactive oxygen species (ROS), The Effects of Tryptanthrin on Microglia nitric oxide (NO) and prostaglandin E2 (PGE2; Streit et al, 2004; More et al, 2013). We confirmed MCAO injury triggers the activation of microglia in brain tissue, and sought to determine whether tryptanthrin influences the function of microglia under LPS-induced inflammatory conditions in vitro
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