Dihydroartemisinin inhibits activation of the Toll-like receptor 4 signaling pathway and production of type I interferon in spleen cells from lupus-prone MRL/lpr mice

Huang, Xueqin; Xie, Zhihua; Liu, Fenfen; Han, Chunwen; Zhang, Dongyu; Wang, Dawei; Bao, Xi; Sun, Jing; Wen, Chengping; Fan, Yongsheng

doi:10.1016/j.intimp.2014.07.001

Cited by 47 publications

(26 citation statements)

References 49 publications

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“…In MRL/lpr mice, SM934 suppressed Th1 and Th17 cell responses, while promoting Treg cell development, by impeding the excessive activation of STAT-1, STAT-3 and STAT-5 [28]. Besides, SM934 interfered with the B cell intrinsic pathway by downregulating TLR7/9 expression, MyD88 expression and NF-kB phosphorylation, which shared similarities with the mechanism of DHA that inhibited activation of the TLR4 signaling pathway [30,35]. In comparison, the therapeutic effects of SM934 on NZB/W F1 mice were tightly linked to enhancing IL-10 production from macrophages, which was absent in MRL/lpr mice [29].…”

Section: Artemisinin Drugs In Systemic Lupus Erythematosus (Sle)mentioning

confidence: 81%

Development of artemisinin drugs in the treatment of autoimmune diseases

Tang

Zuo

2016

Science Bulletin

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Section: Artemisinin Drugs In Systemic Lupus Erythematosus (Sle)mentioning

confidence: 81%

Development of artemisinin drugs in the treatment of autoimmune diseases

Tang

Zuo

2016

Science Bulletin

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“…For example, Hu et al (2011) tested the enrichment of SLE-implicated genes within the 223 expression profiles, and revealed transitional splenic B cells. The pathogenic nature of spleen lymphocytes is also supported by mouse models, and by demonstration of the efficacious nature of spleen cells from lupus-prone MRL/lpr mice targeted therapies ( Huang et al 2014 ; Fleischer et al 2014 ).…”

Section: Discussionmentioning

confidence: 97%

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

Liu

Yin

Wen

et al. 2016

G3 Genes|Genomes|Genetics

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We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE.

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“…For saving millions of lives from malaria-affected populations, Youyou Tu, a Chinese scientist who is best known for identifying artemisinin and DHA, was awarded the 2015 Nobel Prize in Physiology or Medicine. Apart from antimalarial and anti-schistosomiasis [26] activities, DHA has been shown to exhibit inhibitory effects against erythematous lupus [27] , inflammatory diseases [28] , bacteria [29] and viruses [30] . However, another conspicuous property of DHA resides on its potent antitumor activities against a variety of human cancer cells, such as lung carcinoma [31] , breast cancer [32] , hepatocellular carcinoma [33] , osteosarcoma [34] , acute myeloid leukemia [35] and cervical cancer [36] , etc.…”

Section: Signal Transducer and Activator Of Transcription 3 (Stat3)mentioning

confidence: 99%

DHA is a newly defined STAT3 inhibitor that may be of multiple potential uses in cancer treatment

Jia

et al. 2016

Cancer Cell Microenviron

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Accumulating evidence from epidemiological, pharmacological and case control studies has shown that dihydroartemisinin (DHA), one of first-line antimalarial drugs recommended by World Health Organization (WHO), possesses antineoplastic activity and selective cytotoxicity to a variety of human cancer cell model systems. Although some antitumor mechanisms of DHA have been confirmed, the findings from the previous studies are insufficient to fully reveal the whole picture of tumor suppression by DHA. In a recent investigation, we demonstrated that DHA exhibits antitumor properties against a variety of human HNSCC cells both in vitro and in vivo. The underlying mechanism involves selective inhibition of Jak2/STAT3 signaling. By specific inhibition of STAT3 activation, DHA exerted the chemotherapeutic efficacy, including reduction in cell viability and migratory capability, along with induction of G1 phase cell cycle arrest and apoptosis in head and neck squamous cell carcinoma (HNSCC) cells. All of data suggested that DHA may be a potent inhibitor of STAT3 that can be potentially used to treat patients with HNSCC, as well as other human cancers harboring STAT3 activation.

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Dihydroartemisinin inhibits activation of the Toll-like receptor 4 signaling pathway and production of type I interferon in spleen cells from lupus-prone MRL/lpr mice

Cited by 47 publications

References 49 publications

Development of artemisinin drugs in the treatment of autoimmune diseases

Development of artemisinin drugs in the treatment of autoimmune diseases

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

DHA is a newly defined STAT3 inhibitor that may be of multiple potential uses in cancer treatment

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