Cannabidiol modulates type I IFN response genes and HIV infection in macrophages
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201508 | GEO | 2022/09/20
REPOSITORIES: GEO
Similar Datasets
Project description:Cannabis (Cannabis sativa) is a widely used drug in the United States and the frequency of cannabis use is particularly high among people living with HIV (PLWH). One key component of cannabis, the non-psychotropic (-)-cannabidiol (CBD) exerts a wide variety of biological actions, including anticonvulsive, analgesic, and anti-inflammatory effects. However, the exact mechanism of action through which CBD affects the immune cell signaling remains poorly understood. Here we report that CBD modulates type I interferon responses in human macrophages. Transcriptomics analysis shows that CBD treatment significantly attenuates cGAS-STING-mediated activation of type I Interferon response genes (ISGs) in monocytic THP-1 cells. We further showed that CBD treatment effectively attenuates 2'3-cGAMP stimulation of ISGs in both THP-1 cells and primary human macrophages. Interestingly, CBD significantly upregulates expression of autophagy receptor p62/SQSTM1. p62 is critical for autophagy-mediated degradation of stimulated STING. We observed that CBD treated THP-1 cells have elevated autophagy activity. Upon 2'3'-cGAMP stimulation, CBD treated cells have rapid downregulation of phosphorylated-STING, leading to attenuated expression of ISGs. The CBD attenuation of ISGs is reduced in autophagy deficient THP-1 cells, suggesting that the effects of CBD on ISGs is partially mediated by autophagy induction. Lastly, CBD decreases ISGs expression upon HIV infection in THP-1 cells and human primary macrophages, leading to increased HIV RNA expression 24 hours after infection. However, long term culture with CBD in infected primary macrophages reduced HIV viral spread, suggesting potential dichotomous roles of CBD in HIV replication. Our study highlights the immune modulatory effects of CBD and the needs for additional studies on its effect on viral infection and inflammation.
| S-EPMC9560767 | biostudies-literature
Project description:Cannabidiol modulates type I IFN response genes and HIV infection in macrophages
| PRJNA832018 | ENA
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD. Microarray analyses were performed by using three independent sets of control (vehicle-treated) and CBD-treated (10 M-NM-<M, 24-hr) human, immortalized SZ95 sebocytes. The first two sets of the samples were analyzed by two-color microarrays (M-bM-^@M-^\rep1M-bM-^@M-^] and M-bM-^@M-^\rep2M-bM-^@M-^]). Later on, the RNA from the second sample set was used for the M-bM-^@M-^\rep2-1M-bM-^@M-^] hybridization (techical repeat). Finally, we analyzed the third (biological) sample set by using one-color microarray (M-bM-^@M-^\rep3M-bM-^@M-^]).
2014-07-29 | E-GEOD-57571 | biostudies-arrayexpress
Project description:Cannabidiol (CBD), a cannabinoid from the cannabis plant, is widely used in sports for recovery, pain management, and sleep improvement, yet its effects on muscle are not well understood. This study aimed to determine the transcriptional response of murine skeletal muscle myotubes to broad-spectrum CBD and synthetic CBD (sCBD), hypothesizing significant changes in metabolism, myogenesis, and inflammation, with unique gene expression profiles for broad-spectrum CBD due to its additional compounds. Differentiated C2C12 myotubes were treated with 10 µM CBD, sCBD, or vehicle control (DMSO) for 24 hours before RNA extraction. Poly-A tail enriched mRNA libraries were constructed and sequenced using 2x50 bp paired-end sequencing. CBD and sCBD treatment induced 4489 and 1979 differentially expressed genes (DEGs; p <0.001, FDR step-up <0.05), respectively, with common upregulation of 857 genes and common downregulation of 648 genes. Common upregulated DEGs were associated with “response to unfolded protein”, “cell redox homeostasis”, “endoplasmic reticulum stress”, “oxidative stress” and “cellular response to hypoxia”. Common downregulated DEGs were linked to “sarcomere organization”, “skeletal muscle tissue development”, “regulation of muscle contraction”, “skeletal muscle contraction” and “muscle contraction”. CBD treatment induced 1342 unique upregulated DEGs and 1137 unique downregulated DEGs, compared to 154 and 152 unique up- and downregulated DEGs in sCBD. The transcriptional data indicate that CBD may induce mild cellular stress, activating pathways associated with altered redox balance, unfolded protein response, and endoplasmic reticulum stress. We hypothesize that CBD interacts with muscle and may elicit a ‘mitohormetic’ effect that warrants further investigation.
2024-09-25 | GSE272113 | GEO
Project description:Previous studies have shown that cannabis use in people living with HIV-1 is associated with a lower viral load, lower circulating CD16+ monocytes, and high CD4+ T-cell count, suggesting a potential therapeutic application. HIV-1 infected U1 monocytes and primary macrophages were used to assess the effects of CBD in HIV-1 infection. Our data suggests that CBD treatment results in a significant reduction in the number of EVs released from infected cells. Additional findings suggest that this may be mediated by a reduction in viral transcription and autophagy activation. To see the effect of CBD in autophagy activation, U1 and U1 Monocyte Derived Macrophages cells were cultured and lysed. D-Biotin or Biotinylated CBD pull-down from the lysates was performed using Streptavidin-Sepharose beads, which were washed with TNE50 / TNE300 (high salt) + 0.1% NP40 buffers. The complexes were analyzed by mass spectrometry. Reactome enrichment analysis was used to assess the CBD pull-down of HIV-1 infected monocytes (U1) and HIV-1 infected MDM proteins for involvement of the autophagy pathway.
2022-04-04 | PXD027263 | Pride
Project description:IFN-? is a unique type I IFN that is not induced by pattern recognition response elements. IFN-? is constitutively expressed in mucosal tissues, including the female genital mucosa. Although the direct antiviral activity of IFN-? was thought to be weak compared with IFN-?, IFN-? controls Chlamydia muridarum and herpes simplex virus 2 in mice, possibly through modulation of immune response. We show here that IFN-? induces an antiviral state in human macrophages that blocks HIV-1 replication. IFN-? had little or no protective effect in activated CD4+ T cells or transformed cell lines unless activated CD4+ T cells were infected with replication-competent HIV-1 at a low MOI. The block to HIV infection of macrophages was maximal after 24 hours of treatment and was reversible. IFN-? acted on early stages of the HIV life cycle, including viral entry, reverse transcription, and nuclear import. The protection did not appear to operate through known type I IFN-induced HIV host restriction factors, such as APOBEC3A and SAMHD1. IFN-?-stimulated immune mediators and pathways had the signature of type I IFNs but were distinct from IFN-? in macrophages. IFN-? induced significant phagocytosis and ROS, which contributed to the block to HIV replication. These findings indicate that IFN-? induces an antiviral state in macrophages that is mediated by different factors than those induced by IFN-?. Understanding the mechanism of IFN-?-mediated HIV inhibition through immune modulation has implications for prevention.
| S-EPMC5135270 | biostudies-literature
Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD.
2014-07-29 | GSE57571 | GEO
Project description:The non-psychotomimetic phytocannabinoid cannabidiol (CBD) has shown anticonvulsant effects in several seizure models in rats and mice. However, the mechanisms by which CBD exerts its antiepileptic effects are not fully elucidated. MicroRNAs (miRNA) are short non-coding RNAs which regulate protein expression. Dysregulation of miRNAs can contribute to the pathology of various diseases, including epilepsy. This could indicate that the modulation of miRNAs is a potential mechanism of action for the therapeutic effects of CBD. Therefore, we sequenced hippocampal samples from CBD or vehicle treated naive mice to see the effects of CBD on miRNA expression.
2023-07-06 | GSE214761 | GEO
Project description:Over the past few years there has been an increased interest in cannabidiol (CBD) for general use as well as alternative therapeutic for various diseases. Although CBD has only been FDA approved for seizures under the oral formulation, Epidiolex®, the public has used various unregulated forms of CBD to treat a variety of ailments from pain to anxiety and insomnia. Moreover, an increasing subset of CBD advocates take CBD daily to prevent inflammation. This expanded use of CBD strongly suggests that more research is necessary to elucidate the safety and efficacy of CBD and determine the mechanisms by which it acts. Thus, we conducted two separate studies. In the first, RNA sequencing (RNA-Seq) analysis of brains of female mice undergoing experimental autoimmune encephalomyelitis (EAE) in the presence and absence of CBD was conducted in order to identify potential genes that mediated CBD’s neuroprotective effects. In the second, we assessed some of the same genes in male and female mice treated with CBD in the absence of an immune stimulus. Together these data showed that CBD modestly increased oxytocin (Oxt) and vasopressin (Avp) gene expression in the brains of mice, regardless of whether there was active inflammation, suggesting they might serve as biomarkers for CBD exposure, and perhaps, anti-inflammatory efficacy.
2024-07-03 | GSE262437 | GEO
Project description:Cannabidiol (CBD) oral spray on murine oral ulcer significantly inhibited inflammation, relieved pain and accelerated healing process. To gain insight into transcriptional regulation of CBD on cells related to healing progress of oral ulcer, we performed RNA-Seq on the immortalized human oral keratinocyte HOK-16B cell lines stimulated with LPS and ATP, after 10μM CBD or vehicle excipient pretreatment.
2021-07-01 | GSE152088 | GEO