Estrogen and brain inflammation: Effects on microglial expression of MHC, costimulatory molecules and cytokines

ArticleinJournal of Neuroimmunology 161(1-2):123-36 · May 2005with9 Reads
DOI: 10.1016/j.jneuroim.2004.12.016 · Source: PubMed
Abstract
To model the effects of estrogen on adaptive immunity in the brain, we examined the effects of 17beta-estradiol on microglial parameters related to antigen presentation and T cell activation. Specifically, the effects of 17beta-estradiol on basal and LPS-induced surface staining of Class I and II MHC, as well as CD40, CD80, CD86, CD152, CD28, CD8, CD11b, Fas, FasL, and also ERalpha and ERbeta, were examined in N9 microglial cells. Additionally, the effects of 17beta-estradiol on basal and LPS-induced release of cytokines (TNF-alpha, IFN-gamma, IL-2, IL-4, and IL-10) were determined. Data indicate that estrogen increases IL-10 while decreasing TNFalpha and IFNgamma release from resting and LPS-stimulated N9 cells. Additionally, LPS-induced surface staining of MHC Class I, CD40, and CD86 was significantly attenuated by estrogen pretreatment. The basal percentage of cells positive for MHC Class I and II, CD40, and CD152, Fas, and FasL was significantly decreased by estrogen exposure. However, CD8, CD86, CD11b, and CD28 were unaffected by estrogen, and CD80 cell surface staining significantly increased following estrogen exposure. Taken together, these data indicate that estrogen can significantly decrease components of adaptive immunity in microglial cells, and highlight the multi-faceted regulatory effects of estrogen on microglial parameters related to antigen presentation and T cell interaction.
    • "Importantly, estradiol downregulates the expression of proinflammatory molecules in astrocytes (Cerciat et al., 2010; Kipp et al., 2007; Lewis et al., 2008; Nazario Rubio et al., 2011; Valles et al., 2010) by mechanisms involving ERs and the inhibition of nuclear factor (NF) kB signaling (Cerciat et al., 2010; Dodel et al., 1999; Giraud et al., 2010). Estradiol also reduces microglia reactivity (Baker et al., 2004; Bruce-Keller et al., 2001 Dimayuga et al., 2005; Drew and Chavis, 2000; Tapia-Gonzalez et al., 2008; Vegeto et al., 2006). Since inflammatory molecules and microglia regulate the activation of astrocytes (Burda and Sofroniew, 2014), these actions of estradiol may contribute to the hormonal regulation of astrogliosis. "
    [Show abstract] [Hide abstract] ABSTRACT: In the last years there has been a considerable advance in the knowledge on the regulation of astrocytes by sex steroids under physiological and pathological conditions. By the activation of a variety of nuclear and membrane receptors, sex steroid hormones regulate the functions of astrocytes and their communication with other cell types in the central nervous system. Under physiological conditions astrocytes participate in the neuroendocrine and behavioral actions of gonadal steroids, as well as in the hormonal control of brain tissue homeostasis. Under pathological conditions astrocytes mediate, at least partially, the neuroprotective effects of gonadal steroid hormones; given that sex steroids modulate reactive astrogliosis and reduce the release of pro-inflammatory molecules by these cells. Given the side effects that sex steroids may have when administered systemically, a number of synthetic agonists of the receptors for gonadal steroid hormones in the nervous system have been developed, and may be considered for clinical use after brain injury as potential enhancers of the neuroprotective astrocytic functions.
    Full-text · Article · Jun 2016
    • "The neuroprotective and beneficial effects of EST have also been investigated in many cell culture models following free radical or glutamate toxicity in glia and neurons (Sribnick et al., 2004; Das et al., 2005; Sribnick et al., 2009). EST has been shown to induce anti-apoptotic genes and inhibit Ca 2+ influx (Nilsen et al., 2002; Sribnick et al., 2009) and apoptosis (), block calpain activation and activity (Sribnick et al., 2004), and also act as an effective anti-oxidant (Moosmann and Behl, 1999) and anti-inflammatory agent (Dimayuga et al., 2005). EST treatment can shield against a broad span of toxic insults induced by free radicals (Green et al., 1997; Beal, 1998; Brinton et al., 2008), excitotoxicity (Green et al., 1997; Singer et al., 1999; Singh et al., 1999), SCI (Chaovipoch et al., 2006; Li et al., 2007; Yune et al., 2008; Samantaray et al., 2010 Samantaray et al., , 2011), amyloid β (Aβ)-induced toxicity (Chen et al., 2006), and ischemia (Dubal et al., 1998; Green and Simpkins, 2000). "
    [Show abstract] [Hide abstract] ABSTRACT: Estrogen (EST) is a steroid hormone that exhibits several important physiological roles in the human body. During the last few decades, EST has been well recognized as an important neuroprotective agent in a variety of neurological disorders in the central nervous system (CNS), such as spinal cord injury (SCI), traumatic brain injury (TBI), Alzheimer's disease, and multiple sclerosis. The exact molecular mechanisms of EST-mediated neuroprotection in the CNS remain unclear due to heterogeneity of cell populations that express EST receptors (ERs) in the CNS as well as in the innate and adaptive immune system. Recent investigations suggest that EST protects the CNS from injury by suppressing pro-inflammatory pathways, oxidative stress, and cell death, while promoting neurogenesis, angiogenesis, and neurotrophic support. In this review, we have described the currently known molecular mechanisms of EST-mediated neuroprotection and neuroregeneration in SCI and TBI. At the same time, we have emphasized on the recent in vitro and in vivo findings from our and other laboratories, implying potential clinical benefits of EST in the treatment of SCI and TBI.
    Full-text · Article · Oct 2015
    • "Therefore, differing patterns of CD40 expression could contribute to sex differences in the effects of stress on mPFC structure and function, as well as mPFC-mediated behaviors. In vitro studies indicate that both glucocorticoids and estrogens regulate levels of CD40 expression (Dimayuga et al., 2005; Li et al., 2007). Thus, both sex steroids and glucocorticoids could mediate the differential effects of stress on CD40 expression in mPFC. "
    [Show abstract] [Hide abstract] ABSTRACT: Susceptibility to stress-linked psychological disorders, including post-traumatic stress disorder and depression, differs between men and women. Dysfunction of medial prefrontal cortex (mPFC) has been implicated in many of these disorders. Chronic stress affects mPFC in a sex-dependent manner, differentially remodeling dendritic morphology and disrupting prefrontally mediated behaviors in males and females. Chronic restraint stress induces microglial activation, reflected in altered microglial morphology and immune factor expression, in mPFC in male rats. Unstressed females exhibit increased microglial ramification in several brain regions compared to males, suggesting both heightened basal activation and a potential for sex-dependent effects of stress on microglial activation. Therefore, we assessed microglial density and ramification in the prelimbic region of mPFC, and immune-associated genes in dorsal mPFC in male and female rats following acute or chronic restraint stress. Control rats were left unstressed. On the final day of restraint, brains were collected for either qPCR or visualization of microglia using Iba-1 immunohistochemistry. Microglia in mPFC were classified as ramified, primed, reactive, or amoeboid, and counted stereologically. Expression of microglia-associated genes (MHCII, CD40, IL6, CX3CL1, and CX3CR1) was also assessed using qPCR. Unstressed females showed a greater proportion of primed to ramified microglia relative to males, alongside heightened CX3CL1-CX3CR1 expression. Acute and chronic restraint stress reduced the proportion of primed to ramified microglia and microglial CD40 expression in females, but did not significantly alter microglial activation in males. This sex difference in microglial activation could contribute to the differential effects of stress on mPFC structure and function in males versus females.
    Full-text · Article · Oct 2015
Show more