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IL-1 and takayasu

Nikhil Gupta, Jayakanthan Kabeerdoss, Hindhumathi Mohan, Ruchika Goel, Debashish Danda
Introduction: Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls. Materials and Methods: Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited...
2018: Open Rheumatology Journal
Xiufang Kong, Lili Ma, Zongfei Ji, Zhihui Dong, Zhigang Zhang, Jun Hou, Si Zhang, Lingying Ma, Lindi Jiang
OBJECTIVES: This study aimed to clarify potential mechanism of IL-6 involved in adventitial fibrosis via adventitial fibroblast in Takayasu arteritis (TAK). METHODS: Immunohistochemistry and double-labelled immunofluorescence were performed on vascular tissue from patients with TAK and controls. Human aorta adventitial fibroblast (AAF) was cultured and stimulated with interleukine 6 (IL-6)/IL-6 receptor (IL-6R). Real-time PCR, western blot, enzyme-linked immunosorbent assays, chromatin immunoprecipitation (ChIP) and reporter assay were conducted in vitro experiments to determine effect of IL-6/IL-6R on AAF...
July 6, 2017: Clinical and Experimental Rheumatology
Debashish Danda, Ruchika Goel, Sumita Danda, Hindhumathi Mohan, George Joseph, Jayakanthan Kabeerdoss, Swapan K Nath
OBJECTIVES: To assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population. METHODS: In Phase-1, the genomic DNA of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795 (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10) and rs1800468, rs1800469, rs1800470 (transforming growth factor-β). Allele frequencies between cases and controls were compared using chi-squared test and also reassessed empirically (pe) by 10,000 permutations...
July 2017: Human Immunology
Koji Osuka, Yasuo Watanabe, Nobuteru Usuda, Masahiro Aoyama, Kenichiro Iwami, Mikinobu Takeuchi, Takeya Watabe, Masakazu Takayasu
We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from 10 patients during trepanation surgery as the case group, and cerebrospinal fluid (CSF) samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on Day 1 as the control group...
June 1, 2017: Journal of Neurotrauma
Li-Li Pan, Juan Du, Na Gao, Hua Liao, Jin Wan, Wei-Ping Ci, Chun Yang, Tian Wang
Takayasu's arteritis (TAK) is a type of large vessel vasculitis which involves the aorta and its major branches. Interleukin (IL)-9 or IL-9-producing Th9 cells were found to be involved in pathogenesis of autoimmune arteritis such as giant cell arteritis, but IL-9 or Th9 cells in TAK were not well known. Here, this study aims to analyze the levels of serum IL-9 and their major source Th9 cells in TAK. With the help of cytometric bead array (CBA), a total of 21 patients with TAK were examined for serum levels of cytokines IL-4, IL-6, IL-8, IL-17, IL-10, TNF-α, IFN-γ, and IL-9...
December 2016: Clinical Rheumatology
Aichi Niwa, Koji Osuka, Takahiro Nakura, Naoki Matsuo, Takeya Watabe, Masakazu Takayasu
BACKGROUND: Interleukin-6 (IL-6), an inflammatory cytokine, plays important roles in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Chemokines are chemoattractant cytokines that regulate trafficking of monocytes/macrophages and lymphocytes to sites of inflammation. However, no studies have been reported regarding the temporal expression of these cytokines in CSF after SAH. FINDINGS: The concentrations of IL-6, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) in the CSF of ten patients with SAH were measured using ELISA kits over a period of 14 days...
August 30, 2016: Journal of Neuroinflammation
Anne E D Arraes, Alexandre W S de Souza, Henrique A Mariz, Neusa P Silva, Ivone C G Torres, Paula N V Pinto, Eduardo N P Lima, Emilia I Sato
OBJECTIVE: To evaluate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography-computed tomography (PET-CT) and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of (18)F-FDG in arterial walls was determined by PET-CT scans...
July 2016: Revista Brasileira de Reumatologia
Durga Prasanna Misra, Smriti Chaurasia, Ramnath Misra
Introduction. Th17, γδT, NK, and NKT cells in peripheral blood and serum IL-17 and IL-23 in Takayasu arteritis (TA) were measured and correlated with disease activity. Methods. Th17 (anti-CD3APC, CD4PECy7, and IL-17PE), NKT, NK (anti-CD3APC, CD56FITC), and γδT (anti-CD3FITC and γδTCRAPC) cells were enumerated by flow cytometry in peripheral blood of 30 patients with TA (ACR1990 criteria) and 20 healthy controls, serum IL-17 and IL-23 measured by ELISA. Relation with disease activity (NIH criteria, ITAS2010) was analyzed (using nonparametric tests, median with interquartile range)...
2016: Autoimmune Diseases
M Samson, B Bonnotte
Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are two granulomatous vasculitis affecting large arteries that present specific epidemiological and clinical features. Their pathogenesis is not fully understood but major advances have been obtained during the last years, thus allowing the emergence of new therapeutic strategies. GCA and TA develop on a specific genetic background but share some similarities regarding the immunological pathways involved in their pathogenesis. The trigger of these diseases is not clearly identified but it is thought that an infectious agent could activate and lead to the maturation of dendritic cells that are localized in the adventitia of arteries...
April 2016: La Revue de Médecine Interne
Anne E D Arraes, Alexandre W S de Souza, Henrique A Mariz, Neusa P Silva, Ivone C G Torres, Paula N V Pinto, Eduardo N P Lima, Emilia I Sato
OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT)-and serum levels of different cytokines and matrix metalloproteinases (MMPs) in patients with Takayasu's arteritis (TA) and associations with disease activity. METHODS: Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax) of 18F-FDG in arterial walls was determined by PET-CT scans...
July 30, 2015: Revista Brasileira de Reumatologia
Jun Taneo, Takumi Adachi, Aiko Yoshida, Kunio Takayasu, Kazuhiko Takahara, Kayo Inaba
Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia. We prepared Aβ oligomer and fibril from Aβ (1-42) peptide in vitro. We analyzed the characteristics of these oligomers and fibrils by electrophoresis and atomic force microscopy...
March 13, 2015: Biochemical and Biophysical Research Communications
Hao Chen, Donghang Zheng, Sriram Ambadapadi, Jennifer Davids, Sally Ryden, Hazem Samy, Mee Bartee, Eric Sobel, Erbin Dai, Liying Liu, Colin Macaulay, Anthony Yachnis, Cornelia Weyand, Robert Thoburn, Alexandra Lucas
Giant cell arteritis (GCA) and Takayasu's disease are inflammatory vasculitic syndromes (IVS) causing sudden blindness and widespread arterial obstruction and aneurysm formation. Glucocorticoids and aspirin are mainstays of treatment, predominantly targeting T cells. Serp-1, a Myxomavirus-derived serpin, blocks macrophage and T cells in a wide range of animal models. Serp-1 also reduced markers of myocardial injury in a Phase IIa clinical trial for unstable coronary disease. In recent work, we detected improved survival and decreased arterial inflammation in a mouse Herpesvirus model of IVS...
2015: PloS One
D Saadoun, M Garrido, C Comarmond, A C Desbois, F Domont, L Savey, B Terrier, G Geri, M Rosenzwajg, D Klatzmann, P Fourret, P Cluzel, L Chiche, J Gaudric, F Koskas, P Cacoub
OBJECTIVE: Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK. METHODS: T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis...
May 2015: Arthritis & Rheumatology
F Alibaz-Oner, S P Yentür, G Saruhan-Direskeneli, H Direskeneli
OBJECTIVES: Assessment of disease activity is one of the major difficulties in patients with Takayasu arteritis (TAK) during follow-up. To date, no biomarker is universally accepted to be a surrogate for active disease in TAK. In this study, we aimed to investigate levels of various pro-and anti-inflammatory molecules including serum granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, IL-10, IL-18 and IL-23 in patients with TAK. METHODS: The study included 51 patients (age: 40...
March 2015: Clinical and Experimental Rheumatology
Koji Osuka, Yasuo Watanabe, Masahiro Aoyama, Takahiro Nakura, Naoki Matsuo, Masakazu Takayasu
BACKGROUND: IL-6 is a proinflammatory cytokine reported to play an important role in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH). Suppressor of cytokine signaling 3 (SOCS3) is known to act as an inhibitor of signal transduction of IL-6. However, there have been no reports on the expression of SOCS3 in cerebrospinal fluid (CSF) after SAH. FINDINGS: The concentration of IL-6 was measured serially up until day 10, in CSF of eight patients with SAH...
August 14, 2014: Journal of Neuroinflammation
Shin Fukuda, Hitoshi Kohsaka, Aiko Takayasu, Waka Yokoyama, Chie Miyabe, Yoshishige Miyabe, Masayoshi Harigai, Nobuyuki Miyasaka, Toshihiro Nanki
BACKGROUND: Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB(2)) is expressed primarily by immune cells. Theoretically, selective CB(2) agonists should be devoid of psychoactive effects. In this study, we investigated therapeutic effects of a selective CB(2) agonist on arthritis. METHODS: The expression of CB(2) was analyzed with immunohistochemistry and Western blotting...
2014: BMC Musculoskeletal Disorders
Javier Loricera, Ricardo Blanco, Santos Castañeda, Alicia Humbría, Norberto Ortego-Centeno, Javier Narváez, Cristina Mata, Sheila Melchor, Elena Aurrecoechea, Jaime Calvo-Alén, Pau Lluch, Concepción Moll, Mauricio Mínguez, Gabriel Herrero-Beaumont, Beatriz Bravo, Esteban Rubio, Mercedes Freire, Enriqueta Peiró, Carmen González-Vela, Javier Rueda-Gotor, Trinitario Pina, Natalia Palmou-Fontana, Vanesa Calvo-Río, Francisco Ortiz-Sanjuán, Miguel Ángel González-Gay
OBJECTIVES: Non-infectious aortitis is often refractory to standard immunosuppressive therapy. Since IL-6 has been implicated in the pathogenesis of aortitis, we assessed the efficacy of the anti-IL6 receptor monoconal antibody tocilizumab (TCZ) in a series of patients with refractory non-infectious aortitis. METHODS: Review of 16 patients (14 women/2 men) with refractory aortitis diagnosed by imaging (CT angiography, MR angiography, and/or PET) that were treated with TCZ...
May 2014: Clinical and Experimental Rheumatology
Koji Osuka, Nobuteru Usuda, Masahiro Aoyama, Hitoshi Yamahata, Mikinobu Takeuchi, Muneyoshi Yasuda, Masakazu Takayasu
The inflammatory cytokine interleukin-6 (IL-6) plays an important role in causing symptoms of lumbar disk herniation. The present study clarifies the expression of the signaling pathway of IL-6 in herniated discs. Homogenates prepared from lumbar herniated discs from 10 patients were assessed. The expression of janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-STAT3 at Tyr(705), suppressor of cytokine signaling 3 (SOCS3) and actin was examined by Western blot analysis...
May 21, 2014: Neuroscience Letters
Yoshikazu Nakaoka, Kaori Higuchi, Yoh Arita, Michio Otsuki, Kaori Yamamoto, Takahiro Hashimoto-Kataoka, Taku Yasui, Kuniyasu Ikeoka, Tomohito Ohtani, Yasushi Sakata, Yoshihito Shima, Atsushi Kumanogoh, Keiko Yamauchi-Takihara, Toshio Tanaka, Tadamitsu Kishimoto, Issei Komuro
Treatment of refractory Takayasu arteritis (TA) remains an unresolved clinical issue. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose. The aim of the present study was to assess the safety and efficacy of the interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) in patients with TA refractory to conventional therapies including GC. Four patients with TA who had shown GC resistance received TCZ infusions (8 mg/kg) every 4 weeks a total of at least 24 times (range, 24 to 51)...
2013: International Heart Journal
Taryn Youngstein, James E Peters, Shahir S Hamdulay, Devesh Mewar, Alec Price-Forbes, Mark Lloyd, Rachel Jeffery, Anne R Kinderlerer, Justin C Mason
OBJECTIVES: We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. METHODS: Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated...
May 2014: Clinical and Experimental Rheumatology
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