Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signaling and TYK2-Mediated STAT3 Signaling Pathways In Vitro

Suryavanshi, Santosh; Zaiachuk, Mariia; Pryimak, Nazar; Kovalchuk, Igor; Kovalchuk, Olga

doi:10.3390/cells11091391

Cited by 37 publications

(31 citation statements)

References 61 publications

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“…In this work, we focused on the capacity of WIN55,212-2 to impair pro-inflammatory macrophage polarization. Previous studies reported that AEA, 2-AG, THC or CBD inhibit the production of inflammatory mediators in macrophages ( 39 – 41 ). WIN55,212-2 impaired NF-κB activation and cytokine release in LPS-stimulated TLR3/TLR4-transfected HEK293 cells, hmoDCs and murine macrophages activated with oxidized-LDL ( 13 , 42 , 43 ).…”

Section: Discussionmentioning

confidence: 98%

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

et al. 2023

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IntroductionChronic or uncontrolled activation of myeloid cells including monocytes, macrophages and dendritic cells (DCs) is a hallmark of immune-mediated inflammatory disorders. There is an urgent need for the development of novel drugs with the capacity to impair innate immune cell overactivation under inflammatory conditions. Compelling evidence pointed out cannabinoids as potential therapeutic tools with anti-inflammatory and immunomodulatory capacity. WIN55,212-2, a non-selective synthetic cannabinoid agonist, displays protective effects in several inflammatory conditions by mechanisms partially depending on the generation of tolerogenic DCs able to induce functional regulatory T cells (Tregs). However, its immunomodulatory capacity on other myeloid cells such as monocytes and macrophages remains incompletely understood.MethodsHuman monocyte-derived DCs (hmoDCs) were differentiated in the absence (conventional hmoDCs) or presence of WIN55,212-2 (WIN-hmoDCs). Cells were stimulated with LPS, cocultured with naive T lymphocytes and their cytokine production and ability to induce T cell responses were analysed by ELISA or flow cytometry. To evaluate the effect of WIN55,212-2 in macrophage polarization, human and murine macrophages were activated with LPS or LPS/IFNγ, in the presence or absence of the cannabinoid. Cytokine, costimulatory molecules and inflammasome markers were assayed. Metabolic and chromatin immunoprecipitation assays were also performed. Finally, the protective capacity of WIN55,212-2 was studied in vivo in BALB/c mice after intraperitoneal injection with LPS.ResultsWe show for the first time that the differentiation of hmoDCs in the presence of WIN55,212-2 generates tolerogenic WIN-hmoDCs that are less responsive to LPS stimulation and able to prime Tregs. WIN55,212-2 also impairs the pro-inflammatory polarization of human macrophages by inhibiting cytokine production, inflammasome activation and rescuing macrophages from pyroptotic cell death. Mechanistically, WIN55,212-2 induced a metabolic and epigenetic shift in macrophages by decreasing LPS-induced mTORC1 signaling, commitment to glycolysis and active histone marks in pro-inflammatory cytokine promoters. We confirmed these data in ex vivo LPS-stimulated peritoneal macrophages (PMΦs), which were also supported by the in vivo anti-inflammatory capacity of WIN55,212-2 in a LPS-induced sepsis mouse model.ConclusionOverall, we shed light into the molecular mechanisms by which cannabinoids exert anti-inflammatory properties in myeloid cells, which might well contribute to the future rational design of novel therapeutic strategies for inflammatory disorders.

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Section: Discussionmentioning

confidence: 98%

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

et al. 2023

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“…There are interactions between these cytokines, such as IFN- γ, IL-4 and IL-10 may inhibit the production of GM-CSF ( 138 ), and GM-CSF can regulate other cytokine signals (such as IL-1, IL-6, IL-2, IL-8, IL-10, and TNF-α) to influence the inflammatory response ( 139 ). Currently, monoclonal antibodies against a variety of cytokines and a variety of related signaling pathway modulatory agents have shown potential to control the SARS-CoV-2 cytokine storm, such as tocilizumab for IL-6 ( 140 , 141 ), emapalumab for IFN-γ ( 142 ), canakinumab for IL-1β and anakinra for IL-1R ( 143 ), JAK2/STAT3 inhibitors ( 131 , 144 ), NF-κB pathway regulators ( 145 ), MAPK/NF-κB pathway regulators ( 146 ), the nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome signaling inhibitors ( 147 , 148 ). In addition, immunoglobulin ( 149 ), nanotechnology-based corticosteroid drugs ( 150 ), and traditional Chinese medicine ( 151 – 153 ) are also potential drugs to alleviate cytokine storms.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

et al. 2022

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BackgroundSince the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics.MethodsPublications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis.Results1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: “Delta/Omicron variants”, “cytokine storm”, “neutralization/neutralizing antibody”, “T cell”, “BNT162b2”, “mRNA vaccine”, “vaccine effectiveness/safety”, and “long COVID”.ConclusionThis study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.

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“…Toxins and endotoxins produced by pathogens or overgrowth of opportunistic pathogens act to impair and destroy the mucous membrane through a cascade of molecular signals, which is recognized by TLR4 ( 63 ), which presents the signal to MyD88, thereby stimulating the downstream expression of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α). The signaling pathways involved include the classic nuclear transcription factor (NF-kB) or c-Jun N-terminal kinase pathways ( Figure 1B ) which act to up-regulate inflammation and suppress the activity of T regulatory cells (Tregs) ( 64 ), which were partly agreed with the obesity caused by Enterobacter cloacae B29 . Under unfavorable environmental conditions, such as high ammonia concentration, heat, cold, and transportation, animals can suffer abnormal bodily stress.…”

Section: Distinguishing Microbial Differences Associated With Diseasesmentioning

confidence: 99%

Precise strategies for selecting probiotic bacteria in treatment of intestinal bacterial dysfunctional diseases

Yang

Qin²,

Zhang³

2022

Front. Immunol.

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Abundant microbiota resides in the organs of the body, which utilize the nutrition and form a reciprocal relationship with the host. The composition of these microbiota changes under different pathological conditions, particularly in response to stress and digestive diseases, making the microbial composition and health of the hosts body interdependent. Probiotics are living microorganisms that have demonstrated beneficial effects on physical health and as such are used as supplements to ameliorate symptoms of various digestive diseases by optimizing microbial composition of the gut and restore digestive balance. However, the supplementary effect does not achieve the expected result. Therefore, a targeted screening strategy on probiotic bacteria is crucial, owing to the presence of several bacterial strains. Core bacteria work effectively in maintaining microbiological homeostasis and stabilization in the gastrointestinal tract. Some of the core bacteria can be inherited and acquired from maternal pregnancy and delivery; others can be acquired from contact with the mother, feces, and the environment. Knowing the genera and functions of the core bacteria could be vital in the isolation and selection of probiotic bacteria for supplementation. In addition, other supporting strains of probiotic bacteria are also needed. A comprehensive strategy for mining both core and supporting bacteria before its clinical use is needed. Using metagenomics or other methods of estimation to discern the typically differentiated strains of bacteria is another important strategy to treat dysbiosis. Hence, these two factors are significant to carry out targeted isolation and selection of the functional strains to compose the resulting probiotic preparation for application in both research and clinical use. In conclusion, precise probiotic supplementation, by screening abundant strains of bacteria and isolating specific probiotic strains, could rapidly establish the core microbiota needed to confer resilience, particularly in bacterial dysfunctional diseases. This approach can help identify distinct bacteria which can be used to improve supplementation therapies.

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Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signaling and TYK2-Mediated STAT3 Signaling Pathways In Vitro

Cited by 37 publications

References 61 publications

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

Precise strategies for selecting probiotic bacteria in treatment of intestinal bacterial dysfunctional diseases

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