Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways

Kim, Byung-Hak; Na, Kwang-Min; Oh, Ikhoon; Song, Inn-Hye; Lee, Yun Sang; Shin, Jongheon; Kim, Taeyoon

doi:10.1016/j.bcp.2013.01.005

Cited by 47 publications

(37 citation statements)

References 67 publications

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“…The JAK-STAT signaling pathways transduce cytokine-mediated signals and activate JAK-STAT proteins to regulate CD4 + T-cell differentiation and are associated with a wide range of inflammatory diseases. Therefore, regulation of aberrantly activated STAT signaling is important for the treatment of autoimmune disorders (4,20). The strong inhibitory activity of SOD3-transduced MSCs on CD4 + T-cell differentiation was due to the combined effect of its regulation of multiple pathways at various levels, such as the expression of key transcription factors, expression of various proinflammatory cytokines, and activated STAT proteins.…”

Section: Foxp3mentioning

confidence: 99%

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Sah

Kim

Yun

et al. 2016

Antioxidants & Redox Signaling

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Aims: The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. Results: Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as tolllike receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. Innovation and Conclusion: Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression. Antioxid. Redox Signal. 24, 233-248.

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Section: Foxp3mentioning

confidence: 99%

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Sah

Kim

Yun

et al. 2016

Antioxidants & Redox Signaling

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“…To determine the therapeutic potential of BOT-4-one in these diseases, in vivo experiments were performed due to the immunomodulatory activity of BOT-4-one through regulation of CD4 + T cell differentiation into distinct Th-cell subsets. Skin inflammation and autoimmune diseases were induced by topical © 2015 The Society for Investigative Dermatology JID-2015-0249.R2 14 application of TNCB to the skin of mice or intradermal injection with IL-23 into the ears of mice, which are known to induce allergic contact dermatitis, AD-like skin inflammation, and psoriasislike chronic skin inflammation (Takahashi et al, 2005;Kim et al, 2013b;Kim et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice

Lee

Cho

Jeong

et al. 2016

Journal of Investigative Dermatology

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T cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathological immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite multiple pharmacological properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4 T-cell subsets by regulating the expression and production of T cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription (STAT) proteins. In addition, BOT-4-one inhibited T-cell receptor (TCR)-mediated Akt and nuclear factor-kappaB (NF-κB) signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as TNCB-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4 T cell differentiation and the overall immune responses.Journal of Investigative Dermatology accepted article preview online, 30 September 2015. doi:10.1038/jid.2015.384.

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“…Th17 cells act to protect the body against bacterial and fungal infection by producing IL-17, IL-21, and IL-22 (Furuzawa-Carballeda et al, 2007). Additionally, Treg cells play a critical role in the regulation of immune cell homeostasis by producing IL-10 and transforming growth factor-beta (TGF-β) (Kim et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Piper nigrum Fruit Extract Prevents TMA-Induced Allergic Contact Dermatitis by Regulating Th2 Cytokine Production

Jung¹,

Choi²,

Jung³

et al. 2015

JAS

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Allergic contact dermatitis (ACD) remains a leading skin disease in many countries. In this study, we investigated the preventive effect of Piper nigrum fruit extract (PFE) on trimellitic anhydride (TMA)-induced dermatitis and its potential mechanism of action. Oral administration of PFE and prednisolone (PS) significantly suppressed TMA-induced increases in ear, epidermal thickness, and infiltration of CD4 + cells, while abnormal expression of IgE, mMCP-1, IL-1β and IL-1β mRNA was also significantly counteracted by oral administration of PFE. PFE also significantly suppresses TMA-induced IL-4 and IL-5 production and IL-4 mRNA expression in vivo, as well as OVA-induced IL-4, IL-5, and IL-13 production and GATA3 mRNA expression ex vivo, and IL-4 induced STAT6 phosphorylation in primary cultured splenocytes and HaCaT cells. Interestingly, the PFE component piperine significantly suppressed OVA-induced IL-4, IL-5, and IL-13 secretion ex vivo. Taken together, these results suggest that PFE could be useful in suppressing allergic contact dermatitis.

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Kurarinone regulates immune responses through regulation of the JAK/STAT and TCR-mediated signaling pathways

Cited by 47 publications

References 67 publications

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice

Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice

Piper nigrum Fruit Extract Prevents TMA-Induced Allergic Contact Dermatitis by Regulating Th2 Cytokine Production

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