Insights into the modulatory role of cyclosporine A and its research advances in acute inflammation

Gui, Qiuyi; Jiang, Zhijun; Zhang, Luyong

doi:10.1016/j.intimp.2021.107420

Cited by 19 publications

(19 citation statements)

References 96 publications

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“…The binary complex of CypA-CsA then interacts with calcineurin to form a ternary complex, leading to the inhibition of calcineurin and nuclear factor of activated T cells (NFAT), which negatively regu-lates the expression of T-cell-related cytokines (Huai et al, 2002). Based on its regulation on NFAT, CsA is helpful to alleviate autoimmune diseases and acute inflammatory diseases (Gui et al, 2021). Here, we find that the PPIase activity of CypA is required for the enhancement of IL-1b expression (Figures S2J-S2L), but not for the degradation of pro-IL-1b (Figure S3E), suggesting that CsA might relieve acute inflammatory diseases by blocking CypA-enhanced IL-1b expression.…”

Section: Discussionmentioning

confidence: 99%

Delicate regulation of IL-1β-mediated inflammation by cyclophilin A

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Delicate regulation of IL-1β-mediated inflammation by cyclophilin A

et al. 2022

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“…Due to the extreme diversity of infectious microbes as well as tissue structure, it is very reasonable to say that macrophages contain one of the most evolved phenotypic characteristics. 3,[6][7][8] These specialized cells receive various cues from the surrounding environment which allows them to assume different functions and phenotypes. 9 The specificity and complexity of macrophages allow these immune cells to respond in a precise and very specific manner to different stimuli in different tissue types.…”

Section: Impact Statementmentioning

confidence: 99%

“…Macrophages are responsible for digestion of foreign substances through phagocytosis by recognizing LPS present on the surface of certain bacteria. 3,[6][7][8]10 Triterpenoids are naturally occurring compounds extracted from plants. These compounds are steroid-like and are known for their medicinal properties.…”

Section: Impact Statementmentioning

confidence: 99%

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Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

Ahmed

Amin

Sun

et al. 2022

Exp Biol Med (Maywood)

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Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.

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“…Based on its immunosuppressive activity, CsA was widely used in transplantation for organ transplant patients to reduce the risk of organ rejection and effective in alleviating autoimmune diseases, such as spontaneous urticarial ( 9 ), rheumatism ( 10 ) and systemic lupus erythematosus ( 11 ). In addition, substantial evidence shows that CsA is helpful to relieve acute inflammatory diseases, such as sepsis ( 12 – 14 ) and endotoxemia ( 15 ), due to its important role in regulating the functions of innate immune cells (such as monocytes/macrophages, dendritic cells, and neutrophils), vascular activity, the release of cytokines, mitochondrial dysfunction, and apoptosis ( 16 ). Additionally, CsA relieves IAV-induced immunopathological damage ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A

Bai

Yang

et al. 2022

Front. Immunol.

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Cyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of innate immune cells, but the mechanism remains elusive. Here, we investigate the role of CsA in regulating macrophages polarization in influenza A virus-infected mice and mouse bone marrow-derived macrophages. CsA downregulates pro-inflammatory cytokines expression and upregulates anti-inflammatory cytokines expression. Mechanically, CsA decreases the polarization of macrophages into pro-inflammatory M1 phenotype and increases the polarization of macrophages into anti-inflammatory M2 phenotype. Further studies show that CsA regulates macrophages polarization-associated IFN-γ/STAT1 and IL-4/STAT6 signaling pathways. Meanwhile, all these roles of CsA are eliminated when CypA is absent, suggesting that CsA regulates macrophages polarization and inflammatory responses depend on its binding to CypA. Collectively, these results reveal a crucial mechanism of CsA in attenuating IAV-induced inflammatory responses by a switch in macrophages polarization.

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Insights into the modulatory role of cyclosporine A and its research advances in acute inflammation

Cited by 19 publications

References 96 publications

Delicate regulation of IL-1β-mediated inflammation by cyclophilin A

Delicate regulation of IL-1β-mediated inflammation by cyclophilin A

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A

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