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Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
Nidhi Srivastava, Asha Shelly, Manmohan Kumar, Archana Pant, Bhabatosh Das, Tanmay Majumdar, Shibnath Mazumder
Toll-like receptor 4 (TLR4) plays a critical role in host immunity against Gram-negative bacteria. It transduces signals through two distinct TIR-domain-containing adaptors, MyD88 and TRIF, which function at the plasma membrane and endosomes, respectively. Using zebrafish Aeromonas hydrophila infection model, we demonstrate that synchronization of MyD88 and TRIF dependent pathways is critical for determining the fate of infection. Zebrafish were infected with A. hydrophila, and bacterial recovery studies suggested its effective persistence inside the host...
2017: Cell Death Discovery
Hyuk Soon Kim, Seung Taek Nam, Se Hwan Mun, Sun-Kyeong Lee, Hyun Woo Kim, Young Hwan Park, Bokyung Kim, Kyung-Jong Won, Hae-Rim Kim, Yeong-Min Park, Hyung Sik Kim, Michael A Beaven, Young Mi Kim, Wahn Soo Choi
Receptor activator of NF-kB ligand (RANKL) generates intracellular reactive oxygen species (ROS), which increase RANKL-mediated signaling in osteoclast (OC) precursor bone marrow macrophages (BMMs). Here we show that a ROS scavenging protein DJ-1 negatively regulates RANKL-driven OC differentiation, also called osteoclastogenesis. DJ-1 ablation in mice leads to a decreased bone volume and an increase in OC numbers. In vitro, the activation of RANK-dependent signals is enhanced in DJ-1-deficient BMMs as compared to wild-type BMMs...
November 15, 2017: Nature Communications
Min Young Park, Hyung Sik Kim, Mingyu Lee, Byunghyun Park, Ha Young Lee, Eun Bee Cho, Jae Young Seong, Yoe-Sik Bae
Osteoclasts can be differentiated from bone marrow-derived macrophages (BMDM). They play a key role in bone resorption. Identifying novel molecules that can regulate osteoclastogenesis has been an important issue. In this study, we found that FAM19A5, a neurokine or brain-specific chemokine, strongly stimulated mouse BMDM, resulting in chemotactic migration and inhibition of RANKL-induced osteoclastogenesis. Expression levels of osteoclast-related genes such as RANK, TRAF6, OSCAR, TRAP, Blimp1, c-fos, and NFATc1 were markedly decreased by FAM19A5...
November 14, 2017: Scientific Reports
Bin Hui, Liping Zhang, Qinhua Zhou, Ling Hui
Microglia plays a prominent role in the brain's inflammatory response to injury or infection by migrating to affected locations and secreting inflammatory molecules. However, hyperactivated microglial is neurotoxic and plays critical roles in the pathogenesis of neurodegenerative diseases. Pristimerin, a naturally occurring triterpenoid, possesses antitumor, antioxidant, and anti-inflammatory activities. However, the effect and the molecular mechanism of pristimerin against lipopolysaccharide (LPS)-induced neurotoxicity in microglia remain to be revealed...
November 8, 2017: Neurotoxicity Research
Shilin Zhu, Siyuan Tang, Feng Su
Diosgenin, as an essential natural steroidal saponin, can be extracted from numerous sources, primarily from fenugreek. It is an important raw material for the synthesis of steroid hormone drugs. It exhibits antitumor, anti‑inflammatory, antioxidation and several other significant pharmacologic actions, and is of high pharmaceutical value. In the present study, the activities and underlying mechanisms of dioscin in the inhibition of ischemic stroke in rats were investigated. Inflammatory responses wer analyzed using ELISA kits and caspase‑3 and caspase‑9 activity was analyzed using Caspase‑3 and caspase‑9 activity kits...
October 26, 2017: Molecular Medicine Reports
Tao Li, Juan-Juan Qin, Xia Yang, Yan-Xiao Ji, Fangliang Guo, Wen-Lin Cheng, Xiaolin Wu, Fu-Han Gong, Ying Hong, Xue-Yong Zhu, Jun Gong, Zhihua Wang, Zan Huang, Zhi-Gang She, Hongliang Li
Stroke is one of the leading causes of morbidity and mortality worldwide. Inflammation, oxidative stress, apoptosis, and excitotoxicity contribute to neuronal death during ischemic stroke; however, the mechanisms underlying these complicated pathophysiological processes remain to be fully elucidated. Here, we found that the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) was markedly increased after cerebral ischemia/reperfusion (I/R) in mice. TRAF6 ablation in male mice decreased the infarct volume and neurological deficit scores, and decreased pro-inflammatory signaling, oxidative stress and neuronal death after cerebral I/R, whereas transgenic overexpression of TRAF6 in male mice exhibited opposite effects...
November 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Sun Young Jang, Seong Jun Park, Min Kyung Chae, Joon H Lee, Eun Jig Lee, Jin Sook Yoon
AIM: To examine the role of microRNA-146a (miR-146a) in the regulation of fibrosis in an in vitro model of Graves' orbitopathy (GO). METHODS: Orbital fat/connective tissues were harvested from patients with GO and non-GO for primary orbital fibroblast cultures. The effects of transforming growth factor-β (TGF-β), a potent cytokine that promotes fibrosis, on miR-146a expression were analysed in GO and non-GO orbital fibroblasts using quantitative real-time PCR...
November 3, 2017: British Journal of Ophthalmology
Yunfei Qin, Zexiong Su, Yaoxing Wu, Chenglei Wu, Shouheng Jin, Weihong Xie, Wei Jiang, Rongbin Zhou, Jun Cui
MAVS signalosome plays an important role in RIG-I-like receptor (RLR)-induced antiviral signaling. Upon the recognition of viral RNAs, RLRs activate MAVS, which further recruits TRAF6 and other signaling proteins to initiate type I interferon (IFN) activation. MAVS signalosome also regulates virus-induced apoptosis to limit viral replication. However, the mechanisms that control the activity of MAVS signalosome are still poorly defined. Here, we report NLRP11, a Nod-like receptor, is induced by type I IFN and translocates to mitochondria to interact with MAVS upon viral infection...
November 2, 2017: EMBO Reports
Jie Li, Qing Zhou, Xiaojun He, Yongqing Cheng, Dongjin Wang
To explore expression of miR-146b in peripheral blood serum and aortic wall tissues in patients with acute Stanford type A aortic dissection (TAAD), and to discuss the significance and underlying mechanisms.
 Methods: The subjects were divided into a control group (excluded relative aortic diseases) (n=23) and a TAAD group (n=27). The miR-146b levels of serum and aortic wall tissues were detected by quantitative real-time PCR (qRT-PCR). Serum miR-146b and aortic wall tissues miR-146b were compared among different risk TAAD groups...
October 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Yao Lu, Zhou Jiang, Haijiang Dai, Rujia Miao, Jingxian Shu, Haotian Gu, Xing Liu, Zhijun Huang, Guoping Yang, Alex F Chen, Hong Yuan, Ying Li, Jingjing Cai
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent liver pathology marked by hepatic steatosis and commonly accompanied by systematic inflammation and metabolic disorder. Despite an accumulating number of studies, no pharmacological strategy is available to treat this condition in the clinic. The current work applied extensive gain- and loss-of-function approaches to identify the key immune factor leukocyte immunoglobulin-like receptor B4 (LILRB4) as a negative regulator of NAFLD. The hepatocyte-specific knockout of LILRB4 (LILRB4-HKO) significantly exacerbated high-fat diet (HFD)-induced insulin resistance, glucose metabolic imbalance, hepatic lipid accumulation, and systematic inflammation in mice, whereas LILRB4 overexpression in hepatocytes showed a completely opposite phenotype relative to that of LILRB4-HKO mice when compared to their corresponding controls...
November 1, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ke Mao, Wanting Shu, Libin Liu, Qing Gu, Qinghua Qiu, XingWei Wu
BACKGROUNDS: Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. METHODS: C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week...
2017: Oxidative Medicine and Cellular Longevity
Deepthi Nammi, Nagendra S Yarla, Vladimir N Chubarev, Vadim V Tarasov, George E Barreto, Amita Martin Corolina Pasupulati, Gjumrakch Aliev, Nageswara Rao Reddy Neelapu
BACKGROUND: Helicobacter pylori is associated with inflammation of different areas, such as the duodenum and stomach, causing gastritis and gastric ulcers leading to lymphoma and cancer. Pathogenic islands are a type of clustered mobile elements ranging from 10-200 Kb contributing to the virulence of the respective pathogen coding for one or more virulence factors. Virulence factors are molecules expressed and secreted by pathogen and are responsible for causing disease in the host. Bacterial genes/virulence factors of the pathogenic islands represent a promising source for identifying novel drug targets...
October 2017: Current Genomics
Xuemei Liu, Xinyang Zhang, Fengli Wang, Xiao Liang, Zixiu Zeng, Jiayi Zhao, Hong Zheng, Xiangning Jiang, Yunling Zhang
AIM: Kudiezi injection (KDZ) can improve the clinical outcomes of patients with stroke, but the mechanisms remain unclear. This study aimed to investigate whether KDZ could modulate the nuclear factor kappa B (NF-κB) pathways in rat models of transient middle cerebral artery occlusion (tMCAO). MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to tMCAO and randomized to Sham (sham-operated), tMCAO (tMCAO+0.9% saline), and KDZ (tMCAO+7.2mL/kg KDZ) groups...
October 28, 2017: Life Sciences
Prasanna Weeratunga, Thilina U B Herath, Tae-Hwan Kim, Hyun-Cheol Lee, Jae-Hoon Kim, Byeong-Hoon Lee, Eun-Seo Lee, Kiramage Chathuranga, W A Gayan Chathuranga, Chul-Su Yang, Jin Yeul Ma, Jong-Soo Lee
Dense granule protein-7 (GRA-7) is an excretory protein of Toxoplasma gondii. It is a potential serodiagnostic marker and vaccine candidate for toxoplasmosis. Previous reports demonstrated that GRA-7 induces innate immune responses in macrophages by interacting with TRAF6 via the MyD88-dependent pathway. In the present study, we evaluated the antiviral activity and induction of an antiviral state by GRA-7 both in vitro and in vivo. It was observed that GRA-7 markedly reduced the replication of vesicular stomatitis virus (VSV-GFP), influenza A virus (PR8-GFP), coxsackievirus (H3-GFP), herpes simplex virus (HSV-GFP), and adenovirus-GFP in epithelial (HEK293T/HeLa) and immune (RAW264...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
Songwei Ni, Yepin Yu, Jingguang Wei, Lingli Zhou, Shina Wei, Yang Yan, Xiaohong Huang, Youhua Huang, Qiwei Qin
MicroRNA-146a (miR-146a) has been demonstrated to function as a negative regulator of cellular immune responses against pathogens in mammals, however, little information focused on its functions in lower vertebrates. In this study, we investigated the regulatory roles of orange spotted grouper, Epinephelus coioides miR-146a during red spotted grouper nervous necrosis virus (RGNNV) infection. During RGNNV infection in grouper spleen (GS) cells, the endogenous expression level of miR-146a and tumor necrosis factor receptor-associated factor 6 (TRAF6) significantly increased along with the infection time...
October 24, 2017: Fish & Shellfish Immunology
B Alipoor, H Ghaedi, R Meshkani, M D Omrani, Z Sharifi, T Golmohammadi
PURPOSE: Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. METHODS: The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164...
October 22, 2017: Journal of Endocrinological Investigation
Jian-Ping Dai, Qian-Wen Wang, Yun Su, Li-Ming Gu, Ying Zhao, Xiao-Xua Chen, Cheng Chen, Wei-Zhong Li, Ge-Fei Wang, Kang-Sheng Li
Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65...
October 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Zhongrun Qian, Sunhai Zhou, Zhiyi Zhou, Xi Yang, Shuanlin Que, Jin Lan, Yongming Qiu, Yingying Lin
Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often develops quickly and results in tumor recurrence and poor outcome. Recent advances have demonstrated that miRNAs exert critical roles in chemoresistance. Downregulation of miR‑146b‑5p promotes glioma cell proliferation, reduces apoptosis, and correlates with poor survival of patients. Nonetheless, the function of miR‑146b‑5p in temozolomide resistance remains unclear...
September 19, 2017: Oncology Reports
Seung-Ki Min, Sung Youn Jung, Hyun Ki Kang, Sin-A Park, Jong Ho Lee, Myung-Jin Kim, Byung-Moo Min
Numerous studies implicate miR-146a as pleiotropic regulator of carcinogenesis; however, its roles in carcinogenesis are not fully understood. A clue from expression analyses of miR-146a-5p in all 13 oral squamous cell carcinoma (OSCC) cell lines examined and in OSCC tissues, whole blood and whole saliva of OSCC patients in vivo revealed that miR‑146a-5p expression was highly upregulated. Particularly, we widened the view of its upregulation in saliva, implicating that high miR-146a-5p expression is not only correlated closely to the development of human oral cancer, but also to a possible candidate as a diagnostic marker of OSCC...
September 14, 2017: International Journal of Oncology
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