PMID- 37429064 OWN - NLM STAT- MEDLINE DCOM- 20230725 LR - 20230726 IS - 1872-9142 (Electronic) IS - 0161-5890 (Linking) VI - 160 DP - 2023 Aug TI - Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity. PG - 133-149 LID - S0161-5890(23)00136-0 [pii] LID - 10.1016/j.molimm.2023.07.002 [doi] AB - Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4(+) T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-beta-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-kappaB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4(+) cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-kappaB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Zhao, Ge AU - Zhao G AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. FAU - Tong, Yue AU - Tong Y AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. FAU - Xu, Jie AU - Xu J AD - College of Material and Chemical Engineering, Chuzhou University, Chuzhou, Anhui 239000, PR China. FAU - Zhu, Wenjing AU - Zhu W AD - Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, PR China. FAU - Zeng, Jiuseng AU - Zeng J AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. FAU - Liu, Rong AU - Liu R AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. FAU - Luan, Fei AU - Luan F AD - Department of Pharmaceutics, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, PR China. Electronic address: luanfeiren@163.com. FAU - Zeng, Nan AU - Zeng N AD - State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, PR China. Electronic address: 19932015@cdutcm.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230708 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Interleukin-2) RN - 76845O8NMZ (ethyl acetate) RN - 0 (Powders) RN - 0 (NF-kappa B) RN - 0 (Cytokines) RN - 0 (Plant Extracts) SB - IM MH - Animals MH - Mice MH - *Dermatitis, Atopic/drug therapy/chemically induced MH - Interleukin-2 MH - Powders/adverse effects/metabolism MH - NF-kappa B/metabolism MH - Cytokines/metabolism MH - CD4-Positive T-Lymphocytes/metabolism MH - Mice, Inbred BALB C MH - Plant Extracts/pharmacology OTO - NOTNLM OT - Atopic dermatitis OT - IL-2 OT - Jing-Fang powder ethyl acetate extracts OT - NF-kappaB/MAPK pathways OT - T cell activation COIS- Declaration of Competing Interest The authors declare no conflicts of interest. EDAT- 2023/07/10 19:08 MHDA- 2023/07/25 06:42 CRDT- 2023/07/10 18:00 PHST- 2023/04/14 00:00 [received] PHST- 2023/06/24 00:00 [revised] PHST- 2023/07/02 00:00 [accepted] PHST- 2023/07/25 06:42 [medline] PHST- 2023/07/10 19:08 [pubmed] PHST- 2023/07/10 18:00 [entrez] AID - S0161-5890(23)00136-0 [pii] AID - 10.1016/j.molimm.2023.07.002 [doi] PST - ppublish SO - Mol Immunol. 2023 Aug;160:133-149. doi: 10.1016/j.molimm.2023.07.002. Epub 2023 Jul 8.