Effect of a retinoid X receptor partial agonist on airway inflammation and hyperresponsiveness in a murine model of asthma

Published on Jan 23, 2017in Respiratory Research3.924
· DOI :10.1186/S12931-017-0507-Z
Utako Fujii6
Estimated H-index: 6
(Okayama University),
Nobuaki Miyahara33
Estimated H-index: 33
(Okayama University)
+ 9 AuthorsArihiko Kanehiro25
Estimated H-index: 25
(Okayama University)
Sources
Abstract
Background Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners—e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined. The goal of this study is to elucidate the role of RXRs in asthma pathogenesis and the potency of RXR partial agonist in the treatment of allergic airway inflammation and airway hyperresponsiveness using a murine model of asthma.
📖 Papers frequently viewed together
104 Citations
19 Citations
References43
Newest
#1Akihiko Taniguchi (Okayama University)H-Index: 10
#2Nobuaki Miyahara (RMIT: RMIT University)H-Index: 33
Last. Arihiko Kanehiro (Okayama University)H-Index: 25
view all 12 authors...
The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE−/−) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE−/− mice showed reduced eosinophilic inflammation and ...
15 CitationsSource
#1Kondababu Kurakula (UvA: University of Amsterdam)H-Index: 15
#2Mariska Vos (UvA: University of Amsterdam)H-Index: 18
Last. Carlie J.M. de Vries (UvA: University of Amsterdam)H-Index: 35
view all 9 authors...
Allergic asthma is characterized by persistent chronic airway inflammation, which leads to mucus hypersecretion and airway hyperresponsiveness. Nuclear receptor Nur77 plays a pivotal role in distinct immune and inflammatory cells and is expressed in eosinophils and lung epithelium. However, the role of Nur77 in allergic airway inflammation has not been studied so far. In the present study, we determined the role of Nur77 in airway inflammation using a murine model of OVA-induced allergic airway ...
44 CitationsSource
#1Toshiki Kobayashi (Okayama University)H-Index: 3
#2Yuki Furusawa (Okayama University)H-Index: 2
Last. Hiroki KakutaH-Index: 20
view all 12 authors...
RXR partial agonist NEt-4IB (2a, 6-[ethyl-(4-isobutoxy-3-isopropylphenyl)amino]pyridine-3-carboxylic acid: EC50 = 169 nM, Emax = 55%) showed a blood concentration higher than its Emax after single oral administration at 30 mg/kg to mice, and repeated oral administration at 10 mg/kg/day to KK-Ay mice afforded antitype 2 diabetes activity without the side effects caused by RXR full agonists. However, RXR full agonist NEt-3IB (1a), in which the isobutoxy and isopropyl groups of 2a are interchanged,...
13 CitationsSource
#1Kohei Kawata (Okayama University)H-Index: 4
#2Ken Ichi Morishita (Okayama University)H-Index: 5
Last. Hiroki KakutaH-Index: 20
view all 14 authors...
We previously reported RXR partial agonist CBt-PMN (1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid: 5, EC50 = 143 nM, Emax = 75%), which showed a potent glucose-lowering effect without causing serious adverse effects. However, it remains important to elucidate the structural requirements for RXR efficacy and the glucose-lowering effect because RXR-permissive heterodimers such as PPAR/RXR or LXR/RXR are reported to be activated differently depending upo...
23 CitationsSource
#1Chan-Mi Jeon (Korea Research Institute of Bioscience and Biotechnology)H-Index: 10
#2In-Sik Shin (Korea Research Institute of Bioscience and Biotechnology)H-Index: 22
Last. Kyung-Seop Ahn (Korea Research Institute of Bioscience and Biotechnology)H-Index: 24
view all 9 authors...
Abstract Siegesbeckia glabrescens (SG) is a plant growing in Korea that is used as a traditional medicine for various inflammatory diseases. In this study, we investigated the protective effects of SG extract on allergic asthma in an ovalbumin (OVA)-induced asthma murine model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Female BALB/c mice were sensitized by intraperitoneal injection of OVA on days 0 and 14 and then challenged with OVA from days 21 to 23. SG (30 mg/kg) was administere...
30 CitationsSource
#1Ronald M. Evans (Salk Institute for Biological Studies)H-Index: 221
#2David J. Mangelsdorf (UTSW: University of Texas Southwestern Medical Center)H-Index: 131
Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular...
661 CitationsSource
#1Krista McFarland (ACADIA Pharmaceuticals Inc.)H-Index: 8
#2Tracy A. Spalding (ACADIA Pharmaceuticals Inc.)H-Index: 9
Last. Ethan S. BursteinH-Index: 26
view all 6 authors...
Nurr1 is a nuclear hormone receptor (NucHR) strongly implicated in the growth, maintenance, and survival of dopaminergic neurons. Nurr1 may be unable to bind ligands directly, but it forms heterodimers with other NucHRs that do. Using bioluminescence resonance energy transfer (BRET) assays to directly monitor interactions of Nurr1 with other NucHRs, we found the cancer drug bexarotene (Targretin, also LGD1069) displayed biased interactions with Nurr1-RXR heterodimers compared with RXR-RXR homodi...
90 CitationsSource
#1Alessandro Pileri (UNIBO: University of Bologna)H-Index: 59
#2Chiara DelfinoH-Index: 11
Last. Nicola PimpinelliH-Index: 48
view all 4 authors...
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoid neoplasms. The incidence of CTCLs has risen over the last three decades. The most common CTCLs are mycosis fungoides and Sezary syndrome. Therapies for CTCLs are various and range from skin-directed therapy to chemotherapy. Retinoids have been used in CTCL treatment since the 1980s with good results. Bexarotene is the first retinoid approved by the US FDA for CTCL therapy. Since then, numerous experiences of both its effica...
28 CitationsSource
#1Hikari Koga (Okayama University)H-Index: 8
#2Nobuaki Miyahara (Okayama University)H-Index: 33
Last. Arihiko Kanehiro (Okayama University)H-Index: 25
view all 11 authors...
Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and c...
44 CitationsSource
#1William J. Calhoun (UTMB: University of Texas Medical Branch)H-Index: 35
#2Bill T. Ameredes (UTMB: University of Texas Medical Branch)H-Index: 25
Last. Homer A. Boushey (UCSF: University of California, San Francisco)H-Index: 92
view all 35 authors...
Context No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms. Objective To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessmen...
135 CitationsSource
Cited By14
Newest
#1Daisuke Morichika (Okayama University)H-Index: 8
#2Akihiko Taniguchi (Okayama University)H-Index: 10
Last. Masayuki Hanaoka (Shinshu University)H-Index: 28
view all 15 authors...
Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33-/- mice and wild-type (WT) mice were giv...
1 CitationsSource
In this study, human skin fibroblasts human dermis fibroblasts were used as the object, the possible effects and mechanisms of rosemary extract on repeated exposure to Ultraviolet A (UVA) induced senescence of human skin fibroblasts were investigated. During the research, we mainly carried out through two parts. The first part mainly explores the effect of repeated UVA radiation on human skin fibroblasts; the second part mainly discusses the effect of rosemary extract on the induction of human s...
1 CitationsSource
#1Jae-Won Lee (Korea Research Institute of Bioscience and Biotechnology)H-Index: 13
#2Hyung Won Ryu (Korea Research Institute of Bioscience and Biotechnology)H-Index: 21
Last. Sei-Ryang Oh (Korea Research Institute of Bioscience and Biotechnology)H-Index: 34
view all 13 authors...
Abstract Ethnopharmacological relevance Daphne pseudomezereum var. koreana Hamaya is distributed in the Gangwon-do of South Korea and is traditionally used to treat chronic inflammatory diseases, including rheumatoid arthritis. Aim of the study: We investigated the anti-inflammatory effect of biflavonoid-rich fraction (BF) obtained from an extract of D. pseudomezereum leaves on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse model of ovalbumin (OVA)-induced allergic asthma. Ma...
2 CitationsSource
#1Drishti Tiwari (CSIR: Council of Scientific and Industrial Research)H-Index: 5
#2Pawan Gupta (CSIR: Council of Scientific and Industrial Research)H-Index: 25
The escalation in living standards and adoption of ‘Western lifestyle’ has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting towards the critical requirement of organised lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet influences to overal...
2 CitationsSource
#1Ana S. LealH-Index: 10
#2Lyndsey A. ReichH-Index: 2
Last. Karen T. LibyH-Index: 50
view all 5 authors...
Source
#1Ish K MidhaH-Index: 1
#2Nilesh Kumar (Saint Vincent Hospital)H-Index: 1
Last. Taruna Madan (National Institute for Research in Reproductive Health)H-Index: 27
view all 4 authors...
Of all the nutrients, vitamin A has been the most extensively evaluated for its impact on immunity. There are three main forms of vitamin A, retinol, retinal and retinoic acid (RA) with the latter being most biologically active and all-trans-RA (ATRA) its main derivative. Vitamin A is a key regulator of the functions of various innate and adaptive immune cells and promotes immune-homeostasis. Importantly, it augments the interferon-based innate immune response to RNA viruses decreasing RNA virus...
3 CitationsSource
#1Yu Zhang (STU: Shantou University)H-Index: 11
#2Xia Huo (JNU: Jinan University)H-Index: 36
Last. Xijin Xu (STU: Shantou University)H-Index: 33
view all 6 authors...
Abstract Heavy metals generate adverse health effects by interfering with immune homeostasis and promoting inflammation in individuals. Our objective was to explore the induction of immune and inflammatory responses by multiple heavy metals in children living in the e-waste contaminated area. A total of 147 preschool children were recruited, including 73 children from Guiyu, a typical e-waste recycling area, and 74 from a reference group. Blood levels of heavy metals, including lead (Pb), cadmiu...
11 CitationsSource
#1Wang ZhiwangH-Index: 1
#2Nan YaoH-Index: 1
Last. Mei GuoH-Index: 1
view all 9 authors...
Abstract Butylphthalide (NBP) is a phthalide compound contained in Angelicae Sinensis Radix which is one of the most widely used traditional Chinese medicines. This study aims to explore the therapeutic effect of NBP on airway inflammation, mucus hypersecretion and their possible mechanism in asthma mice. BALB/c mice were sensitized and challenged with ovalbumin (OVA) for establishment of asthma model and then treated with NBP during day 22–77. The pulmonary function of the mice was determined, ...
4 CitationsSource
#1Naohiro Oda (Okayama University)H-Index: 8
#2X. Nobuaki Miyahara (RMIT: RMIT University)H-Index: 1
Last. Yoshinobu Maeda (Okayama University)H-Index: 29
view all 11 authors...
Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y...
8 CitationsSource
#1Daisuke Morichika (Okayama University)H-Index: 8
#2Nobuaki Miyahara (Okayama University)H-Index: 33
Last. Arihiko Kanehiro (Okayama University)H-Index: 25
view all 12 authors...
Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome proliferator-activated receptors. The NR family may also play important roles in the development of emphysema. However, the role of RXRs in the pathogenesis of emphysema is not well defined. We dev...
12 CitationsSource