Curcumin Inhibits CD4<SUP>+</SUP> T Cell Activation, but Augments CD69 Expression and TGF-β1-Mediated Generation of Regulatory T Cells at Late Phaseopen access
- Authors
- Kim, Girak; Jang, Mi Seon; Son, Young Min; Seo, Min Ji; Ji, Sang Yun; Han, Seung Hyun; Jung, In Duk; Park, Yeong-Min; Jung, Hyun Jung; Yun, Cheol-Heui
- Issue Date
- Apr-2013
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.8, no.4
- Journal Title
- PLOS ONE
- Volume
- 8
- Number
- 4
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/72121
- DOI
- 10.1371/journal.pone.0062300
- ISSN
- 1932-6203
- Abstract
- Background: Curcumin is a promising candidate for a natural medicinal agent to treat chronic inflammatory diseases. Although CD4(+) T cells have been implicated in the pathogenesis of chronic inflammation, whether curcumin directly regulates CD4(+) T cells has not been definitively established. Here, we showed curcumin-mediated regulation of CD2/CD3/CD28-initiated CD4(+) T cell activation in vitro. Methodology/Principal Findings: Primary human CD4(+) T cells were stimulated with anti-CD2/CD3/CD28 antibody-coated beads as an in vitro surrogate system for antigen presenting cell-T cell interaction and treated with curcumin. We found that curcumin suppresses CD2/CD3/CD28-initiated CD4(+) T cell activation by inhibiting cell proliferation, differentiation and cytokine production. On the other hand, curcumin attenuated the spontaneous decline of CD69 expression and indirectly increased expression of CCR7, L-selectin and Transforming growth factor-beta 1 (TGF-beta 1) at the late phase of CD2/CD3/CD28-initiated T cell activation. Curcumin-mediated up-regulation of CD69 at late phase was associated with ERK1/2 signaling. Furthermore, TGF-beta 1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. Conclusions/Significance: Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4(+) T cell activation by augmenting CD69, CCR7, L-selectin and TGF-beta 1 expression followed by regulatory T cell generation. These results suggest that curcumin could directly reduce T cell-dependent inflammatory stress by modulating CD4(+) T cell activation at multiple levels.
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