title: Potent ameliorating effect of Hypoxia-inducible factor 1α (HIF-1α) antagonist YC-1 on combined allergic rhinitis and asthma syndrome (CARAS) in Rats.
abstract: Recent studies have implicated that Hypoxia-inducible factor 1α (HIF-1α) plays an integral role in the pathogenesis of allergic rhinitis and asthma. In the present study, we showed that HIF-1α antagonist YC-1, 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole, elicited a potent allergy-ameliorating effect in a rat model of ovalbumin (OVA)-sensitized combined allergic rhinitis and asthma syndrome (CARAS). We revealed that YC-1 administration markedly impaired the total number and percentage of eosinophil in bronchoalveolar lavage fluid (BAL Fluid) of the rats, suggesting that YC-1 might attenuate lung and nasal mucosal inflammation in OVA-sensitized rats. Moreover, histological examination found that OVA-induced pathological alterations were evidently attenuated following YC-1 administration. In addition, immunohistochemistrial analysis indicated that YC-1 treatment decreased the expression of HIF-1α in rat lungs and nasal mucosa. Notably, Nuclear factor kappa B (NF-κB) p65 and Peroxisome proliferator-activated receptor α (PPARα), two important regulators of inflammatory responses, were also significantly down-regulated following YC-1 administration. Real-time PCR analysis confirmed that YC-1 impaired the expression of HIF-1α, NF-κB and PPARα in CARAS model. These findings together indicated that YC-1 exerted remarkable anti-allergic effects through the modulation of inflammatory pathways, implying that YC-1 may potentially serve as a novel anti-CARAS medicine in clinical patients.
authors: Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
authors: Xu
authors: X
authors: Wang
authors: Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
authors: Chun
authors: C
authors: Liu
authors: Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
authors: Liucheng
authors: L
authors: Wu
authors: Laboratory Animals Center, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China. Electronic address: zsx@ntu.edu.cn.
authors: Shunxing
authors: S
authors: Zhu
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D007191:Indazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D065631:Rhinitis, Allergic / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D047493:PPAR alpha; D012333:RNA, Messenger; D051996:Transcription Factor RelA; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D010047:Ovalbumin
keywords: Combined allergic rhinitis and asthma syndrome; HIF-1α; Inflammation; Rat; YC-1