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il 17 inhibition

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https://www.readbyqxmd.com/read/28220116/cpg-odn-shapes-alum-adjuvant-activity-signaling-via-myd88-and-il-10
#1
Luciana Mirotti, Ricardo Wesley Alberca Custódio, Eliane Gomes, Florencia Rammauro, Eliseu Frank de Araujo, Vera Lucia Garcia Calich, Momtchilo Russo
Aluminum-containing adjuvants usually referred as Alum are considered as T helper type-2 (Th2) adjuvants, while agonists of toll-like receptors (TLRs) are viewed as adjuvants that favor Th1/Th17 immunity. Alum has been used in numerous vaccine formulations; however, its undesired pro-Th2 adjuvant activity constitutes a caveat for Alum-based vaccines. Combining Alum with TLR-dependent, pro-Th1/Th17 adjuvants might dampen the pro-Th2 activity and improve the effectiveness of vaccine formulations. Here, using the ovalbumin (OVA) model of allergic lung inflammation, we found that sensitization with the synthetic TLR9 agonist, which is composed of oligodeoxynucleotides containing CpG motifs adsorbed to Alum, inhibited the development of OVA-induced lung allergic Th2 responses without shifting toward a Th1 pattern...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219902/ndr1-protein-kinase-promotes-il-17-and-tnf-%C3%AE-mediated-inflammation-by-competitively-binding-traf3
#2
Chunmei Ma, Wenlong Lin, Zhiyong Liu, Wei Tang, Rahul Gautam, Hui Li, Youcun Qian, He Huang, Xiaojian Wang
Interleukin 17 (IL-17) is an important inducer of tissue inflammation and is involved in numerous autoimmune diseases. However, how its signal transduction is regulated is not well understood. Here, we report that nuclear Dbf2-related kinase 1 (NDR1) functions as a positive regulator of IL-17 signal transduction and IL-17-induced inflammation. NDR1 deficiency or knockdown inhibits the IL-17-induced phosphorylation of p38, ERK1/2, and p65 and the expression of chemokines and cytokines, whereas the overexpression of NDR1 promotes IL-17-induced signaling independent of its kinase activity...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219695/inhibitory-effects-of-dynorphin-3-14-on-the-lipopolysaccharide-induced-toll-like-receptor-4-signalling-pathway
#3
Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells...
February 17, 2017: Peptides
https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#4
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#5
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28199730/fentanyl-suppresses-the-survival-of-cd4-t-cells-isolated-from-human-umbilical-cord-blood-through-inhibition-of-ikks-mediated-nf-%C3%AE%C2%BAb-activation
#6
Kun Ma, Pengyu Ma, Huaihai Lu, Shuxiang Liu, Qinying Cao
The aim of this study was to investigate the effects and the underlying mechanisms of fentanyl anesthetic on T lymphocytes isolated from human umbilical cord bloodin vitro. The percentages of CD4(+) , CD8(+) , and regulatory T (Treg) cells in human umbilical cord blood mononuclear cells (UBMC) treated with fentanyl in vitrowere analyzed by flow cytometry. The levels of cytokines IFN-γ, IL-2, IL-4, and IL-17 secreted by activated CD4(+) T cells were measured by ELISA assays. Expressions of MAPK and NF-κB signaling pathway proteins were determined by Western blotting...
February 15, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28194607/il-17a-monoclonal-antibody-partly-reverses-the-glucocorticoids-insensitivity-in-mice-exposed-to-ozonec
#7
Xia Fei, Peng-Yu Zhang, Xue Zhang, Guo-Qing Zhang, Wu-Ping Bao, Ying-Ying Zhang, Min Zhang, Xin Zhou
Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0...
February 13, 2017: Inflammation
https://www.readbyqxmd.com/read/28194046/morinda-citrifolia-noni-fruit-juice-reduces-inflammatory-cytokines-expression-and-contributes-to-the-maintenance-of-intestinal-mucosal-integrity-in-dss-experimental-colitis
#8
Beatriz Coutinho de Sousa, Juliana Reis Machado, Marcos Vinicius da Silva, Thiago Alvares da Costa, Javier Emilio Lazo-Chica, Thatiane do Prado Degasperi, Virmondes Rodrigues Junior, Helioswilton Sales-Campos, Elizabeth Uber Bucek, Carlo José Freire Oliveira
Morinda citrifolia L. (noni) has been shown to treat different disorders. However, data concerning its role in the treatment of intestinal inflammation still require clarification. In the current study, we investigated the effects of noni fruit juice (NFJ) in the treatment of C57BL/6 mice, which were continuously exposed to dextran sulfate sodium (DSS) for 9 consecutive days. NFJ consumption had no impact on the reduction of the clinical signs of the disease or on weight loss. Nonetheless, when a dilution of 1 : 10 was used, the intestinal architecture of the mice was preserved, accompanied by a reduction in the inflammatory infiltrate...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28193225/the-active-metabolite-of-leflunomide-a77-1726-attenuates-inflammatory-arthritis-in-mice-with-spontaneous-arthritis-via-induction-of-heme-oxygenase-1
#9
Su-Jin Moon, Eun-Kyung Kim, Joo Yeon Jhun, Hee Jin Lee, Weon Sun Lee, Sang-Hi Park, Mi-La Cho, Jun-Ki Min
BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28188801/astragalus-polysaccharides-protect-against-dextran-sulfate-sodium-induced-colitis-by-inhibiting-nf-%C3%AE%C2%BA%C3%B0-activation
#10
Jun Lv, Yahong Zhang, Zhiqiang Tian, Fang Liu, Ying Shi, Yao Liu, Peiyuan Xia
Astragalus polysaccharide (APS) is a bioactive extract of Astragalus membranaceus (AM), which possess a wide range of medicinal benefits, including anti-inflammatory, anti-oxidative, anti-tumor and anti-diabetic effects. The present work evaluated the therapeutic effect of APS and its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The APS treatment led to significant improvements in colitis disease activity index (DAI) and histological scores, as well as significantly increased weight and colon length in mice as compared to the control group...
February 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28187456/inhibition-and-deficiency-of-the-immunoproteasome-subunit-lmp7-suppress-the-development-and-progression-of-colorectal-carcinoma-in-mice
#11
Julia Koerner, Thomas Brunner, Marcus Groettrup
New treatment options and drug targets for colorectal carcinoma are a pressing medical need. Inflammation and pro-inflammatory cytokines produced by Th1 and Th17 cells like IL-6, TNF, IL-17 and IL-23 promote the development and growth of colorectal cancer (CRC). The immunoproteasome is a proteasome subtype highly expressed in immune cells but also in the intestine. Since the immunoproteasome promotes Th1 and Th17 differentiation and pro-inflammatory cytokine production, we investigated here whether deficiency or inhibition of the immunoproteasome subunit LMP7 would interfere with CRC development and exacerbation in preventive and therapeutic mouse models...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186160/3-bromopyruvate-ameliorate-autoimmune-arthritis-by-modulating-th17-treg-cell-differentiation-and-suppressing-dendritic-cell-activation
#12
Takaichi Okano, Jun Saegusa, Keisuke Nishimura, Soshi Takahashi, Sho Sendo, Yo Ueda, Akio Morinobu
Recent studies have shown that cellular metabolism plays an important role in regulating immune cell functions. In immune cell differentiation, both interleukin-17-producing T (Th17) cells and dendritic cells (DCs) exhibit increased glycolysis through the upregulation of glycolytic enzymes, such as hexokinase-2 (HK2). Blocking glycolysis with 2-deoxyglucose was recently shown to inhibit Th17 cell differentiation while promoting regulatory T (Treg) cell generation. However, 2-DG inhibits all isoforms of HK. Thus, it is unclear which isoform has a critical role in Th17 cell differentiation and in rheumatoid arthritis (RA) pathogenesis...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184939/interleukin-17a-promotes-esophageal-adenocarcinoma-cell-invasiveness-through-ros-dependent-nf-%C3%AE%C2%BAb-mediated-mmp-2-9-activation
#13
Dong Liu, Rong Zhang, Jie Wu, Yansong Pu, Xiaoran Yin, Yan Cheng, Jing Wu, Cheng Feng, Yumei Luo, Jun Zhang
Interleukin-17A (IL-17A), a pro-inflammatory cytokine secreted primarily by Th17 cells, has been proved to be involved in the microenvironment of certain inflammation-related tumors. However, the role of IL-17A in cancer development has always been controversial. In this study, we investigated the effect of IL-17A on the regulation of esophageal adenocarcinoma (EAC) cell invasiveness and related molecular mechanism. Surface IL-17 receptor (IL-17R) expression on human EAC cell line OE19 was examined using flow cytometry...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28167631/ex-th17-nonclassical-th1-cells-are-functionally-distinct-from-classical-th1-and-th17-cells-and-are-not-constrained-by-regulatory-t-cells
#14
Sharee A Basdeo, Deborah Cluxton, Jamal Sulaimani, Barry Moran, Mary Canavan, Carl Orr, Douglas J Veale, Ursula Fearon, Jean M Fletcher
Th17 cells are an important therapeutic target in autoimmunity. However, it is known that Th17 cells exhibit considerable plasticity, particularly at sites of autoimmune inflammation. Th17 cells can switch to become ex-Th17 cells that no longer produce IL-17 but produce IFN-γ. These ex-Th17 cells are also called nonclassical Th1 cells because of their ability to produce IFN-γ, similar to Th1 cells; however, it is unclear whether they resemble Th1 or Th17 cells in terms of their function and regulation, and whether they have a pathogenic role in autoimmunity...
February 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28167114/an-antisense-peptide-nucleic-acid-against-pseudomonas-aeruginosa-inhibiting-bacterial-induced-inflammatory-responses-in-the-cystic-fibrosis-ib3-1-cellular-model-system
#15
Giulia Montagner, Valentino Bezzerri, Giulio Cabrini, Enrica Fabbri, Monica Borgatti, Ilaria Lampronti, Alessia Finotti, Peter E Nielsen, Roberto Gambari
Discovery of novel antimicrobial agents against Pseudomonas aeruginosa able to inhibit bacterial growth as well as the resulting inflammatory response is a key goal in cystic fibrosis research. We report in this paper that a peptide nucleic acid (PNA3969) targeting the translation initiation region of the essential acpP gene of P. aeruginosa, and previously shown to inhibit bacterial growth, concomitantly also strongly inhibits PAO1 induced up-regulation of the pro-inflammatory markers IL-8, IL-6, G-CSF, IFN-γ, IP-10, MCP-1 and TNF-α in IB3-1 cystic fibrosis cells infected by P...
February 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28166793/cytotoxic-t-cells-modulate-inflammation-and-endogenous-opioid-analgesia-in-chronic-arthritis
#16
Uta Baddack-Werncke, Melanie Busch-Dienstfertig, Sara González-Rodríguez, Santhosh Chandar Maddila, Jenny Grobe, Martin Lipp, Christoph Stein, Gerd Müller
BACKGROUND: This study examined the development of chronic pain, a cardinal symptom of rheumatoid arthritis (RA), in mice with antigen- and collagen-induced arthritis (ACIA). Since the role of CD8(+) T cells in arthritis is controversial, we investigated the consequences of CD8-depletion on arthritis development and opioid modulation of pain in this novel model of chronic autoimmune arthritis. METHODS: Disease severity in control and CD8-depleted animals was determined by histological assessment of knee-joint sections and measurement of autoantibody formation...
February 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28165543/effect-of-nucleoside-analogues-in-the-treatment-of-hepatitis-b-cirrhosis-and-its-effect-on-th17-cell
#17
J Zhang, H Ying, L Wei, L-J Hong
OBJECTIVE: We conducted this study to analyze the effects of nucleoside analogues in the treatment of hepatitis B cirrhosis and its effect on Th17 cells. PATIENTS AND METHODS: 120 patients were randomly divided into lamivudine combined with adefovir dipivoxil group (combined group) and entecavir group. There were 59 cases in the combined group and 59 cases in entecavir group. The combined group was administered lamivudine 100 mg/d + adefovir dipivoxil 10 mg/d and entecavir group was administered entecavir 0...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#18
Han Zhang, Yuanyuan Qi, Yuanyang Yuan, Li Cai, Haiyan Xu, Lili Zhang, Bing Su, Hong Nie
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28160571/the-oncoprotein-gankyrin-promotes-the-development-of-colitis-associated-cancer-through-activation-of-stat3
#19
Toshiharu Sakurai, Hiroaki Higashitsuji, Hiroshi Kashida, Tomohiro Watanabe, Yoriaki Komeda, Tomoyuki Nagai, Satoru Hagiwara, Masayuki Kitano, Naoshi Nishida, Takaya Abe, Hiroshi Kiyonari, Katsuhiko Itoh, Jun Fujita, Masatoshi Kudo
Although long-standing colonic inflammation due to refractory inflammatory bowel disease (IBD) promotes the development of colitis-associated cancer (CAC), the molecular mechanisms accounting for the development of CAC remains largely unknown. In this study, we investigated the role of gankyrin in the development of CAC since gankyrin is overexpressed in sporadic colorectal cancers. We analyzed gene expression of colon tissues obtained from 344 patients with IBD and CAC and found that expression of gankyrin was much higher in colonic mucosa of patients with refractory IBD than in those with IBD in remission...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28160109/antimetastatic-pectic-polysaccharide-from-decalepis-hamiltonii-galectin-3-inhibition-and-immune-modulation
#20
Sathisha U Venkateshaiah, Mallikarjuna S Eswaraiah, Harish Nayaka M Annaiah, Shylaja M Dharmesh
Melanoma is a malignant neoplasm of major concern because of its high mortality rate and failure of chemotherapy. Previously we have shown that galectin-3, a galactose specific lectin, plays a pivotal role in the initiation of metastasis. It was hypothesized that blocking galectin-3 with galactose rich dietary pectic polymer would inhibit metastasis. The current study analyzes the preventive effect and mode of action of a pectic polymer from Swallow Root (Decalepis hamiltonii) in a preventative study of B16F10 cells lung colonization...
February 3, 2017: Clinical & Experimental Metastasis
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