Curcumin inhibits CD4(+) T cell activation, but augments CD69 expression and TGF-β1-mediated generation of regulatory T cells at late phase

• Published in: PloS one Vol. 8; no. 4; p. e62300
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.04.2013; Public Library of Science (PLoS)
• Subjects: Agricultural biotechnology; Agriculture; Animal sciences; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antibodies - pharmacology; Antigen-presenting cells; Antigens; Antigens, CD - genetics; Antigens, CD - immunology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - immunology; Apoptosis; Beads; Biology; Blood & organ donations; CCR7 protein; CD2 antigen; CD28 antigen; CD3 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD69 antigen; Cell activation; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chemistry; Curcumin; Curcumin - pharmacology; Disease; Gene Expression Regulation - drug effects; Humans; Immunoglobulins; Immunoregulation; In vitro methods and tests; Inflammation; Inflammatory diseases; Kinases; L-selectin; L-Selectin - genetics; L-Selectin - immunology; Lectins, C-Type - agonists; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Life sciences; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Medical research; Medicine; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - immunology; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - immunology; Pathogenesis; Primary Cell Culture; Receptors, CCR7 - genetics; Receptors, CCR7 - immunology; Review boards; Signal Transduction; Signaling; Stem cells; T cell receptors; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Transforming growth factor; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1; Zoology; United States > US; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0062300

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. 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-β1 (TGF-β1) 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-β1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4(+) T cell activation by augmenting CD69, CCR7, L-selectin and TGF-β1 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.