Cucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound. Here, its effects on CD4(+) T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system, were investigated. Production of major pathogenic Th cell cytokines: interferon-gamma and interleukin-17 were inhibited under the influence of CucE. The effects of CucE on CD4(+) T cells were mediated through the modulation of aryl hydrocarbon receptor, STAT3, NFκB, p38 MAPK, and miR-146 signaling. Further, production of nitric oxide and reactive oxygen species, as well as phagocytic ability, were inhibited in macrophages treated with CucE. These results imply that CucE possesses powerful antiencephalitogenic activity.
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http://dx.doi.org/10.1021/acs.jafc.6b00951 | DOI Listing |
Cell Rep
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address:
Proteasomes generate antigenic peptides presented on cell surfaces-a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations.
View Article and Find Full Text PDFEBioMedicine
January 2025
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China. Electronic address:
Background: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.
Methods: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens.
J Clin Invest
December 2024
Université Paris Cité, CNRS, INSERM, Institut Necker Enfants Malades-INEM, Paris, France.
Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), the pathophysiology of which remains unclear and for which there is no definitive cure. Antimicrobial peptides (AMPs) are immunomodulatory molecules expressed in various tissues, including the CNS. Here, we investigated whether the cathelicidin-related AMP (CRAMP) modulated the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
View Article and Find Full Text PDFJ Neuroinflammation
November 2024
Department of Medicine, Section of General Pathology, University of Verona, Strada le Grazie 8, 37134, Verona, Italy.
Background: Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation.
Methods: We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells.
Immunohorizons
September 2024
Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT.
Although T cells are encephalitogenic during demyelinating disease, B cell-depleting therapies are a successful treatment for patients with multiple sclerosis. Murine models of demyelinating disease utilizing myelin epitopes, such as myelin oligodendrocyte glycoprotein (MOG)35-55, induce a robust CD4 T cell response but mitigate the contribution of pathological B cells. This limits their efficacy for investigating how B cell depletion affects T cells.
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