Methamphetamine modulates the production of interleukin-6 and tumor necrosis factor-alpha via the cAMP/PKA/CREB signaling pathway in lipopolysaccharide-activated microglia

Wang, Biao; Chen, Teng; Wang, Jing; Jia, Yuwei; Ren, Hai‐Peng; Wu, Feng; Hu, M H; Chen, Yanjiong

doi:10.1016/j.intimp.2018.01.024

Cited by 34 publications

(24 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2A,B). In addition, Meth has been shown to modulate cytokine secretion by regulating a cAMP/PKA/CREB signaling pathway in microglial cells 31 . We observed significant increases in cAMP at 30 minutes after Meth treatment indicating that Meth can activate cAMP mediated signaling pathways in CD4 + T-cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our study showed that Meth significantly increased intracellular [Ca 2+ ] and cAMP levels in CD4 + T-cells. Meth is known to induce increased cytosolic calcium concentration flux and cAMP release in neuronal cells 20,31 . Both of these pathways play major roles in T-cell signaling and activation, and are involved in downstream regulation of the transcription factors NFκB, CREB and NFAT1 32 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Methamphetamine functions as a novel CD4+ T-cell activator via the sigma-1 receptor to enhance HIV-1 infection

Prasad

Kulkarni

Shrivastava

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Methamphetamine (Meth) exacerbates HIV-1 pathobiology by increasing virus transmission and replication and accelerating clinical progression to AIDS. Meth has been shown to alter the expression of HIV-1 co-receptors and impair intrinsic resistance mechanisms of immune cells. However, the exact molecular mechanisms involved in augmenting HIV-1 replication in T-cells are still not yet clear. Here, we demonstrate that pretreatment with Meth of CD4+ T-cells enhanced HIV-1 replication. We observed upregulation of CD4+ T-cell activation markers and enhanced expression of miR-34c-5p and miR-155 in these cells. Further, we noted activation of the sigma-1 receptor and enhanced intracellular Ca2+ concentration and cAMP release in CD4+ T-cells upon Meth treatment, which resulted in increased phosphorylation and nuclear translocation of transcription factors NFκB, CREB, and NFAT1. Increased gene expression of IL-4 and IL-10 was also observed in Meth treated CD4+ T-cells. Moreover, proteasomal degradation of Ago1 occurred upon Meth treatment, further substantiating the drug as an activator of T-cells. Taken together, these findings show a previously unreported mechanism whereby Meth functions as a novel T-cell activator via the sigma-1 signaling pathway, enhancing replication of HIV-1 with expression of miR-34c-5p, and transcriptional activation of NFκB, CREB and NFAT1.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Methamphetamine functions as a novel CD4+ T-cell activator via the sigma-1 receptor to enhance HIV-1 infection

Prasad

Kulkarni

Shrivastava

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Recent studies have also shown an upregulation of microglial C/EBP-β upon pro-inflammatory stimulation (Dasgupta et al, 2003; Ejarque-Ortiz et al, 2007, 2010). MA as a widely abused psychoactive drug, induced microglial activation and secretion of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α (Wang et al, 2018). Pro-inflammatory cytokines IL-1β, IL-6, or TNF-α and LPS induced C/EBP-β upregulation in microglia through activation of the mitogen-activated protein kinases (MAPKs) signaling pathway (Ejarque-Ortiz et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Role of C/EBP-β in Methamphetamine-Mediated Microglial Apoptosis

Chen

Zhao

et al. 2019

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Methamphetamine (MA) is a widely abused psychoactive drug that primarily damages the nervous system. However, the involvement of MA in the survival of microglia remains poorly understood. CCAAT-enhancer binding protein (C/EBP-β) is a transcription factor and an important regulator of cell apoptosis. Lipocalin2 (lcn2) is a known apoptosis inducer and is involved in many cell death processes. We hypothesized that C/EBP-β is involved in MA-induced lcn2-mediated microglial apoptosis. To test this hypothesis, we measured the protein expression of C/EBP-β after MA treatment and evaluated the effects of silencing C/EBP-β or lcn2 on MA-induced apoptosis in BV-2 cells and the mouse striatum after intrastriatal MA injection. MA exposure increased the expression of C/EBP-β and stimulated the lcn2-mediated modulation of apoptosis. Moreover, silencing the C/EBP-β-dependent lcn2 upregulation reversed the MA-induced microglial apoptosis. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-C/EBP-β into the striatum ameliorated the MA-induced decrease survival of microglia. These findings provide a new insight regarding the specific contributions of C/EBP-β-lcn2 to microglial survival in the context of MA abuse.

show abstract

“…Thioperamide, a histamine H3R antagonist, also suppresses in ammatory cell recruitment after ischemic events through histamine dependent mechanism [34]. In addition, activation of H3R downstream signaling CREB, which is involved in improving cognitive dysfunction and Aβ pathology in AD [35,36], could also suppresses in ammatory response [37][38][39] through inhibiting the activation of glial cells [40][41][42]. Nevertheless, whether CREB-mediated anti-in ammation and inactivation of glial cells are involved in the alleviated cognitive de cit and Aβ pathology by H3R antagonist in AD remains undetermined.…”

Section: Page 4/47mentioning

confidence: 99%

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Wang

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundAlzheimer's disease (AD) is an age-related neurodegenerative disease, which characterized by deposition of amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and accompanied by neuroinflammation. Neuroinflammatory processes are well acknowledged to contribute to the progression of AD pathology. Histamine H3 receptor (H3R) is a presynaptic autoreceptor regulating histamine release via negative feedback way. H3R antagonist has been reported to have anti-inflammatory efficacy. However, whether inhibition of H3R is responsible for the anti-neuroinflammation and neuroprotection on APP/PS1 Tg mice remains unclear. MethodsIn this study, microgliosis, astrogliosis, A1 type astrocytes and A2 type astrocytes in APP/PS1 Tg mice were measured by immunostaining by Iba1, GFAP, C3 and S100A10 with and without treatment of thioperamide, an H3R antagonist. Inflammatory response of APP/PS1 Tg mice and effects of thioperamide were studied by measuring levels of pro-inflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) and anti-inflammatory cytokines (interleukin-4 [IL-4]). Protein levels of p-CREB and p-P65 NF-kB was tested by western blot to study the mechanism of thioperamide on AD. H89 was applied to study whether the mechanism offered by thioperamide was dependent on CREB activating. The effect of thioperamide and H89 on Aβ deposition was measured by immunostaining and ELISA. The cognitive function was tested by novel object recognition, Y maze and morris water maze. ResultsInhibition of H3R by thioperamide reduced the gliosis and induced a phenotypical switch from A1 to A2 in astrocytes, and ultimately attenuated neuroinflammation in APP/PS1 Tg mice. Additionally, thioperamide rescued the decrease of cyclic AMP response element-binding protein (CREB) phosphorylation and suppressed the phosphorylated nuclear factor kappa B (NF-κB) in APP/PS1 Tg mice. H89, an inhibitor of CREB signaling, abolished these effects of thioperamide to suppress gliosis and proinflammatory cytokine release. Lastly, thioperamide alleviated the deposition of Aβ and cognitive dysfunction in APP/PS1 mice, which were both reversed by administration of H89. ConclusionsTaken together, these results suggested the H3R antagonist thioperamide improved cognitive impairment in APP/PS1 Tg mice via modulation of the CREB-mediated gliosis and inflammation inhibiting, which contributed to Aβ clearance. This study uncovered a novel mechanism involving inflammatory regulating behind the therapeutic effect of thioperamide in AD.

show abstract

Methamphetamine modulates the production of interleukin-6 and tumor necrosis factor-alpha via the cAMP/PKA/CREB signaling pathway in lipopolysaccharide-activated microglia

Cited by 34 publications

References 69 publications

Methamphetamine functions as a novel CD4+ T-cell activator via the sigma-1 receptor to enhance HIV-1 infection

Methamphetamine functions as a novel CD4+ T-cell activator via the sigma-1 receptor to enhance HIV-1 infection

Role of C/EBP-β in Methamphetamine-Mediated Microglial Apoptosis

Inhibition of Histamine H3 receptor Attenuates Neuroinflammation and Cognitive Impairments in Alzheimer’s Disease via activating CREB Pathway

Contact Info

Product

Resources

About