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The cannabinoid agonist WIN55,212-2 (WIN) suppresses the inflammation-associated transcriptional response of astrocytes to interleukin 1 beta

ABSTRACT: Accumulating evidence suggest that the endocannabinoid system is an attractive target to attenuate inflammatory responses that are implicated in neurodegeneration. Alterations in astrocytic functions play a crucial role in neuroinflammation as a consequence of the loss of their neuroprotective role or the gain of their toxic inflammatory properties. In this study, we explore the possible immunosuppressive action of the cannabinoid receptor agonist WIN55,212-2 using an in vitro model of primary human astrocytes that are activated by the pro-inflammatory cytokine interleukin 1 beta (IL1B). Genome-wide transcriptomic analysis using RNA-seq revealed that the pretreatment of astrocytic cultures with WIN55, 212-2 prevents the transcriptional activation of pro-inflammatory genes induced by IL1B. We report the immunosuppressive function of WIN55,212-2 in replicates RNA samples that were extracted from human astrocyte cultures established from one donor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160092 | GEO | 2021/01/01

REPOSITORIES: GEO

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Project description:Staphylococcus Enterotoxin B (SEB) is an exotoxin produced by Staphylococcus aureus. It is a public health threat during nosocomial infections. It is also considered as a biological weapon. The Centers for Disease Control and Prevention (CDC) lists SEB as a category B agent of Biodefence. SEB is easily aerosolized and can enter the host through inhalation which could lead to Acute Lung Injury (ALI) and in severe cases, it may result in multiple organ failure, shock and death. It is considered to be a Super-antigen as it activates a large number (30%) of T cells and results in the production of cytokines SEB binds directly to the non polymorphic region of MHC Class II which is expressed on antigen presenting cells and this complex activates T cells expressing a specific variable region of the β chain (Vβ8) of the T cell receptor (TCR). Thus, inhalation of SEB leads to recruitment of immune cells into the lung and secretion of pro-inflammatory cytokines which results in severe damage to the lung by increasing the permeability, and induction of respiratory failure. MicroRNA (miRNAs) is considered one of the mechanisms by which the epigenetic regulation happens. MicroRNA are noncoding small RNAs that have recently been shown to play a role in gene expression. The action of miRNA is dependent on its binding to 3’ Untranslated Region (3’UTR) of mRNA resulting in transcriptional or translational repression. Specifically, the efficacy of gene silencing is determined by the interaction of miRNA seed sequence with the target mRNA. Endocannabinoids are lipid molecules produced endogenously by host cells and bind to cannabinoid receptors, CB1 and CB2. N-Arachidonoylethanolamide or anandamide (AEA) is an endocannabinoid that has been shown to have immunomodulatory effects by our lab and others, although the precise mechanism is not clear. So far through my research, I found that Endocannabinoid is involved in a very unique way in the anti-inflammatory response through upregulation of many anti-inflammatory genes such as FOXP3, ARG1, and IL-10 that targeted by miRNA23a-3p and miRNA 34a-5p as well as the anti-inflammatory phenotype population as it show in the RT-PCR and flow cytometry results.

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The cannabinoid agonist WIN55,212-2 (WIN) suppresses the inflammation-associated transcriptional response of astrocytes to interleukin 1 beta

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