CELL
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2019
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IF 36.216
Ke-qi Fan,Yi-yuan Li,Hao-li Wang,Xin-tao Mao,Jin-xin Guo,Fei Wang,Ling-jie Huang,Yi-ning Li,Xiang-yu Ma,Zheng-jun Gao,Wei Chen,Dan-dan Qian,Wen-jin Xue,Qian Cao,Lei Zhang,Li Shen,Long Zhang,Chao Tong,Jiang-yan Zhong,Wei Lu,Ling Lu,Ke-ming Ren,Guisheng Zhong,Yuan Wang,Mingliang Tang,Xin-Hua Feng,Ren-jie Chai,Jin Jin
Summary Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4 + T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4 + T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4 + T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4 + T cells. Our study implicates a critical link between a purine metabolic disorder in CD4 + T cells and stress-driven anxiety-like behavior.
研究领域:
免疫学
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神经科学
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分子生物学
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行为科学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Cheng Lu,ShiJun Deng,YanJiao Liu,ShengJin Yang,DingMei Qin,LiJuan Zhang,Rui-rui Wang,Yi Zhang
Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.
研究领域:
药理学
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免疫学
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皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2020
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IF 4.873
Liu Tang,Xiao-Lei Li,Zi-Xin Deng,Yao Xiao,Ya-Hong Cheng,Jing Li,Hong Ding
Conjugated linoleic acid (CLA), commonly found in beef, lamb and dairy products, has been reported to exhibit anti-inflammatory and antipruritus effects and to inhibit the release of chemical mediators such as histamine and eicosanoid in laboratory rodents. The chief objective of the study is to assess the efficacy of CLA on atopic dermatitis (AD) in mice and to explore possible mechanisms with CLA treatments . To develop a new therapy for AD, the anti-AD potential of CLA was investigated by inducing AD-like skin lesions in mice using 2,4-dinitrofluorobenzene. We evaluated dermatitis severity; histopathological changes; serum levels of T helper (Th) cytokines (interferon-γ, interleukin-4); changes in protein expression by western blotting and immunohistochemistry staining for cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), toll like receptor 4 (TLR-4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB) and tumor necrosis factor α (TNF-α); and production of the proinflammatory lipid mediators, such as prostaglandin E 2 and leukotriene B4 , in the skin lesions. Treatment with CLA ameliorated the development of AD-like clinical symptoms and effectively inhibited epidermal hyperplasia and infiltration of mast cells and CD4 + T cells in the AD mouse skin. Total serum immunoglobulin E levels and the expression levels of Th1/Th2 cytokines and lipid mediators in dorsal skin were dramatically suppressed by CLA. Furthermore, CLA down-regulated the expressions of COX-2, 5-LOX, TLR4, MyD88, NF-κB and TNF-α. Taken together, our findings demonstrate the potential usefulness of CLA as an anti-inflammatory dietary supplement or drug for the prevention and management of AD skin diseases by modulating the COX-2/5-LOX and TLR4/MyD88/NF-κB signaling pathways .
研究领域:
免疫学
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药理学
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皮肤科
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
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2023
·
IF 3.3
Chijing Zuo,Yan Liu,Jie Wang,Weidong Yu,Yujie Liu,Yanyan Zhang,Jingjing Xu,Daiyin Peng,Can Peng
Compound diclofenac sodium chlorphenamine maleate tablets (CDCT) are widely used for the cold in Asia. However, CDCT can cause hematuria symptoms in clinical, and the underlying mechanism is unknown. This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites and further explore the possible mechanisms of CDCT-induced nephrotoxicity. Sprague–Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6 days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen, and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolites, such as succinate, leukotriene B 4 (LTB 4 ), and cardiolipin (CL), are observed in the CDCT-induced nephrotoxicity. Functionally, succinate accumulation leads to mitochondrial damage, as evidence by the imbalance of complex I and complex II and an increase in mitochondrial reactive oxygen species (mito SOX). Meanwhile, LTB 4 activated the NF-κB signaling, as shown by increased protein of p65, phosphor-p65, and decreased protein of IκBα and phosphor-IκBα. Eventually, the apoptosis pathway was triggered in response to reduced CL, inflammation, and mito SOX, as demonstrated by the expression of cyt c, Bax, Bcl-2, caspase-3, and caspase-9. This study indicated that CDCT-induced metabolic disorders triggered nephrotoxicity and provided a comprehensive information to elucidate the mechanism of CDCT induced nephrotoxicity.
研究领域:
药理学
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毒理学
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代谢组学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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