title: Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.
abstract: Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Hefei Yigong Medicine Co., Ltd., Hefei 230088, Anhui, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jie
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China. Electronic address: wylcpu625@163.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000097:blood / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007267:Injections; D016209:Interleukin-8 / Q000097:blood; D017336:Loratadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016328:NF-kappa B / Q000378:metabolism*; D017817:Nasal Lavage Fluid / Q000166:cytology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D065631:Rhinitis, Allergic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018926:Anti-Allergic Agents; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; D006634:Histamine H1 Antagonists; D016209:Interleukin-8; D016328:NF-kappa B; D017336:Loratadine; D006632:Histamine; D010047:Ovalbumin; D048049:Extracellular Signal-Regulated MAP Kinases; C121345:desloratadine
keywords: Allergic rhinitis; Anti-allergic; Anti-inflammatory; Chemokine; Desloratadine citrate disodium injection (DLC)