title: Curcumin inhibits CD4(+) T cell activation, but augments CD69 expression and TGF-β1-mediated generation of regulatory T cells at late phase.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Girak
authors: G
authors: Kim
authors: Mi Seon
authors: MS
authors: Jang
authors: Young Min
authors: YM
authors: Son
authors: Min Ji
authors: MJ
authors: Seo
authors: Sang Yun
authors: SY
authors: Ji
authors: Seung Hyun
authors: SH
authors: Han
authors: In Duk
authors: ID
authors: Jung
authors: Yeong-Min
authors: YM
authors: Park
authors: Hyun Jung
authors: HJ
authors: Jung
authors: Cheol-Heui
authors: CH
authors: Yun
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D000099192:CD69 Antigens
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003474:Curcumin; D019041:L-Selectin; D037181:Lectins, C-Type; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D054400:Receptors, CCR7; D053773:Transforming Growth Factor beta1; D000099192:CD69 Antigens; C515370:CCR7 protein, human; C535150:MAPK1 protein, human
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