Dataset Information

Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-?B signaling pathway.

ABSTRACT: Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo. Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice. DHA also dose-dependently suppressed proliferation of lymphocytes induced by lipopolysaccharide and concanavalin A. DHA inhibited binding of C-X-C chemokine ligand 10 (CXCL10) and its receptor (C-X-C motif) receptor 3 (CXCR3), thus inhibiting calcium flow. DHA can also reduce expression levels of PI3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, nuclear factor (NF)-?B/p65, and p-NF-?B/p65. In conclusion, DHA may serve as treatment drug for AIT by inhibiting the CXCR3/PI3K/AKT/NF-kB signaling pathway.

SUBMITTER: Liu H

PROVIDER: S-EPMC5777751 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-κB signaling pathway.

Liu Huijuan H Tian Qin Q Ai Xiaoyu X Qin Yuan Y Cui Zhanhong Z Li Meng M Yang Jiahuan J Zhai Denghui D Liu Yanrong Y Chen Shuang S Meng Jing J Sun Tao T Zhou Honggang H Yang Cheng C

Oncotarget 20171201 70

Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT <i>in vitro</i> and <i>in vivo</i>. Results showed that DHA can visibly reduce antithyroglobulin ant ...[more]

PMID: 29383139

Similar Datasets

Project description:BackgroundNeuroinflammation and blood-brain barrier (BBB) disruption are two critical mechanisms of subarachnoid hemorrhage (SAH)-induced brain injury, which are closely related to patient prognosis. Recently, angiogenic factor with G-patch and FHA domain 1 (Aggf1) was shown to inhibit inflammatory effect and preserve vascular integrity in non-nervous system diseases. This study aimed to determine whether Aggf1 could attenuate neuroinflammation and preserve BBB integrity after experimental SAH, as well as the underlying mechanisms of its protective roles.MethodsTwo hundred forty-nine male Sprague-Dawley rats were subjected to the endovascular perforation model of SAH. Recombinant human Aggf1 (rh-Aggf1) was administered intravenously via tail vein injection at 1 h after SAH induction. To investigate the underlying neuroprotection mechanism, Aggf1 small interfering RNA (Aggf1 siRNA) and PI3K-specific inhibitor LY294002 were administered through intracerebroventricular (i.c.v.) before SAH induction. SAH grade, neurological score, brain water content, BBB permeability, Western blot, and immunohistochemistry were performed.ResultsExpression of endogenous Aggf1 was markedly increased after SAH. Aggf1 was primarily expressed in endothelial cells and astrocytes, as well as microglia after SAH. Administration of rh-Aggf1 significantly reduced brain water content and BBB permeability, decreased the numbers of infiltrating neutrophils, and activated microglia in the ipsilateral cerebral cortex following SAH. Furthermore, rh-Aggf1 treatment improved both short- and long-term neurological functions after SAH. Meanwhile, exogenous rh-Aggf1 significantly increased the expression of PI3K, p-Akt, VE-cadherin, Occludin, and Claudin-5, as well as decreased the expression of p-NF-?B p65, albumin, myeloperoxidase (MPO), TNF-?, and IL-1?. Conversely, knockdown of endogenous Aggf1 aggravated BBB breakdown, inflammatory response and neurological impairments at 24 h after SAH. Additionally, the protective roles of rh-Aggf1 were abolished by LY294002.ConclusionsTaken together, exogenous Aggf1 treatment attenuated neuroinflammation and BBB disruption, improved neurological deficits after SAH in rats, at least in part through the PI3K/Akt/NF-?B pathway.

Dataset Information

Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-?B signaling pathway.

Publications

Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-κB signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure