Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2: Its Implication for Vitiligo Treatment.
Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon (IFN)-γ-induced phosphorylation of JAK2 and its downstream signal transducer and activator of transcription (STAT)1 and STAT3 in a dose-dependent manner. We further examined the chemoattractant expression in melanocytes and demonstrated that EGCG significantly inhibited IFN-γ-induced expression of intracellular adhesion molecule (ICAM)-1, CXCL10, and monocyte chemotactic protein (MCP)-1 in human melanocytes. In addition, EGCG reduced the protein levels of the corresponding receptors including CD11a, CXCR3, and CCR2 in human T lymphocytes. As a consequence, adhesion of human T cells to melanocytes induced by IFN-γ was effectively suppressed by EGCG. Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.
Department of Dermatology, Guangxing Affiliated Hospital of Zhejiang Chinese Medical University.
Weixuan
W
Ning
Suiquan
S
Wang
Xiaowu
X
Dong
Dongyin
D
Liu
Lifang
L
Fu
Rong
R
Jin
Aie
A
Xu
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D040881:CD11a Antigen / Q000378:metabolism; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D054390:Receptors, CCR2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014820:Vitiligo / Q000188:drug therapy* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C515334:CCR2 protein, human; D040881:CD11a Antigen; D010936:Plant Extracts; D054390:Receptors, CCR2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate; C507924:JAK2 protein, human; D053614:Janus Kinase 2