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Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes.
- Source :
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International Immunopharmacology . Jan2022, Vol. 102, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- [Display omitted] • Taraxasterol (TAS) mitigates concanavalin A (Con A)-induced hepatitis in mice. • TAS reduces IL-2 secretion in Con A-treated mice and Con A-stimulated lymphocytes. • TAS reduces the expression of IL-2Rɑ (CD25) on lymphocytes upon Con A stimulation. • TAS suppresses IL-2/IL-2R signaling in lymphocytes involving NF-κB, PDK1 and STAT3/5. Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 102
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 154244205
- Full Text :
- https://doi.org/10.1016/j.intimp.2021.108380