PMID- 28114934 OWN - NLM STAT- MEDLINE DCOM- 20171130 LR - 20181113 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 18 IP - 1 DP - 2017 Jan 23 TI - Effect of a retinoid X receptor partial agonist on airway inflammation and hyperresponsiveness in a murine model of asthma. PG - 23 LID - 10.1186/s12931-017-0507-z [doi] LID - 23 AB - 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. METHODS: We investigated the effect of a novel RXR partial agonist (NEt-4IB) on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in a murine model of asthma. Balb/c mice were sensitized (days 0 and 14) and challenged (days 28-30) with ovalbumin (OVA), and airway inflammation and airway responses were monitored 48 h after the last OVA challenge. NEt-4IB was administered orally on days 25 to 32. RESULTS: Oral administration of NEt-4IB significantly suppressed AHR and inflammatory cell accumulation in the airways and attenuated the levels of TNF-alpha in the lung and IL-5, IL-13 and NO levels in bronchoalveolar lavage (BAL) fluid and the number of periodic acid Schiff (PAS)-positive goblet cells in lung tissue. Treatment with NEt-4IB also significantly suppressed NF-kappaB expression. CONCLUSION: These data suggest that RXRs may be of crucial importance in the mechanism of allergic asthma and that the novel RXR partial agonist NEt-4IB may be a promising candidate for the treatment of allergic airway inflammation and airway hyperresponsiveness in a model of allergic asthma. FAU - Fujii, Utako AU - Fujii U AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Miyahara, Nobuaki AU - Miyahara N AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Taniguchi, Akihiko AU - Taniguchi A AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Oda, Naohiro AU - Oda N AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Morichika, Daisuke AU - Morichika D AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Murakami, Etsuko AU - Murakami E AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Nakayama, Hikari AU - Nakayama H AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Waseda, Koichi AU - Waseda K AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Kataoka, Mikio AU - Kataoka M AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Kakuta, Hiroki AU - Kakuta H AD - Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 1-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan. FAU - Tanimoto, Mitsune AU - Tanimoto M AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. FAU - Kanehiro, Arihiko AU - Kanehiro A AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. akanehir@md.okayama-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170123 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (Anti-Asthmatic Agents) RN - 0 (Retinoid X Receptors) SB - IM MH - Animals MH - Anti-Asthmatic Agents/administration & dosage MH - Asthma/*drug therapy/*immunology MH - Bronchial Hyperreactivity/*drug therapy/*immunology MH - Female MH - Mice MH - Mice, Inbred BALB C MH - Pneumonia/*drug therapy/*immunology MH - Retinoid X Receptors/agonists/*immunology MH - Treatment Outcome PMC - PMC5260083 OTO - NOTNLM OT - Animal model OT - Asthma OT - NF-kappaB OT - Nitric oxide OT - RXR OT - RXR partial agonist EDAT- 2017/01/25 06:00 MHDA- 2017/12/01 06:00 PMCR- 2017/01/23 CRDT- 2017/01/25 06:00 PHST- 2016/10/25 00:00 [received] PHST- 2017/01/13 00:00 [accepted] PHST- 2017/01/25 06:00 [entrez] PHST- 2017/01/25 06:00 [pubmed] PHST- 2017/12/01 06:00 [medline] PHST- 2017/01/23 00:00 [pmc-release] AID - 10.1186/s12931-017-0507-z [pii] AID - 507 [pii] AID - 10.1186/s12931-017-0507-z [doi] PST - epublish SO - Respir Res. 2017 Jan 23;18(1):23. doi: 10.1186/s12931-017-0507-z.