Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization

Li, Maoquan; Wang, Yanyan; Guo, R. S.; Bai, Yun; Yu, Zhengping

doi:10.1016/j.imlet.2007.02.002

Cited by 29 publications

(21 citation statements)

References 51 publications

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“…Clearly, the use of immunosuppressive or immunomodulatory therapies to reduce microglial activity could constitute one such clinically relevant approach. In this regard, the corticosteroid DEX is commonly prescribed as an immunosuppressive therapy following injuries to the CNS [40,41] and acts by inhibiting microglial proliferation [42], reducing their migratory capabilities [43] and potentially increasing microglial apoptosis [44,45]. In keeping with this role of DEX in vivo, we observed a significant reduction in the numbers of microglia in slice lesion sites.…”

Section: Discussionsupporting

confidence: 70%

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

2016

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Development of nanoparticle (NP) based therapies to promote regeneration in sites of central nervous system (CNS; i.e. brain and spinal cord) pathology relies critically on the availability of experimental models that offer biologically valid predictions of NP fate in vivo. However, there is a major lack of biological models that mimic the pathological complexity of target neural sites in vivo, particularly the responses of resident neural immune cells to NPs. Here, we have utilised a previously developed in vitro model of traumatic spinal cord injury (based on 3-D organotypic slice arrays) with dynamic time lapse imaging to reveal in real-time the acute cellular fate of NPs within injury foci. We demonstrate the utility of our model in revealing the well documented phenomenon of avid NP sequestration by the intrinsic immune cells of the CNS (the microglia). Such immune sequestration is a known translational barrier to the use of NP-based therapeutics for neurological injury. Accordingly, we suggest that the utility of our model in mimicking microglial sequestration behaviours offers a valuable investigative tool to evaluate strategies to overcome this cellular response within a simple and biologically relevant experimental system, whilst reducing the use of live animal neurological injury models for such studies.

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Section: Discussionsupporting

confidence: 70%

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

2016

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“…182 Glucocorticoids can suppress ischemia-induced microglial activation in vivo 183 and prevent microglia from inducing T-cell proliferation and Th1 responses. 184 However, this anti-inflammatory effect has not been shown to consistently reduce brain injury in experimental studies, and in some studies it worsened injury. 185 These discrepancies may be due to other effects of glucocorticoids, such as potentiation of excitotoxicity and impaired glucose transport into neurons.…”

Section: Glucocorticoidsmentioning

confidence: 99%

Microglial Activation in Stroke: Therapeutic Targets

2010

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Summary:Microglial activation is an early response to brain ischemia and many other stressors. Microglia continuously monitor and respond to changes in brain homeostasis and to specific signaling molecules expressed or released by neighboring cells. These signaling molecules, including ATP, glutamate, cytokines, prostaglandins, zinc, reactive oxygen species, and HSP60, may induce microglial proliferation and migration to the sites of injury. They also induce a nonspecific innate immune response that may exacerbate acute ischemic injury. This innate immune response includes release of reactive oxygen species, cytokines, and proteases. Microglial activation requires hours to days to fully develop, and thus presents a target for therapeutic intervention with a much longer window of opportunity than acute neuroprotection. Effective agents are now available for blocking both microglial receptor activation and the microglia effector responses that drive the inflammatory response after stroke. Effective agents are also available for targeting the signal transduction mechanisms linking these events. However, the innate immune response can have beneficial as well deleterious effects on outcome after stoke, and a challenge will be to find ways to selectively suppress the deleterious effects of microglial activation after stroke without compromising neurovascular repair and remodeling.

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“…59 Corticotropin-releasing hormone was shown to exert proapoptotic activity in microglial cells through activation of the caspase-3 pathway and the mitochondrial pathway associated with the generation of ROS by mitochondria and caspase-9 activation. 60 The immune signaling (antigen-presenting) function of microglial cells may be affected by glucocorticoid interruption of expressions of MHC class I and II 61,62 and interleukins. 62,63 Corticosteroids act upon microglial cells by binding to glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs).…”

Section: Corticosteroids and Microgliamentioning

confidence: 99%

“…60 The immune signaling (antigen-presenting) function of microglial cells may be affected by glucocorticoid interruption of expressions of MHC class I and II 61,62 and interleukins. 62,63 Corticosteroids act upon microglial cells by binding to glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). Steroid receptor distribution and activity in microglial cells was shown in detail by Sierra et al 64 According to their study, microglial cells represent a direct target for steroid hormones because of rich expressions of GRs, MRs, and estrogen receptor alpha.…”

Section: Corticosteroids and Microgliamentioning

confidence: 99%

Intravitreous Delivery of the Corticosteroid Fluocinolone Acetonide Attenuates Retinal Degeneration in S334ter-4 Rats

Glybina

Kennedy

Ashton

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization

Cited by 29 publications

References 51 publications

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

Microglial Activation in Stroke: Therapeutic Targets

Intravitreous Delivery of the Corticosteroid Fluocinolone Acetonide Attenuates Retinal Degeneration in S334ter-4 Rats

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