title: Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation.
abstract: Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway inflammation by regulating chemokine expression. In a mouse allergic asthma model, we found that mRNA expression of intelectin-2 as well as MCP-1 and -3 in mouse lung was increased very early (within 2 h) after allergen challenge. Expression of intelectin protein was localized to mucous cells in airway epithelium. Treatment of MLE12 mouse lung epithelial cells with interleukin IL-13, a critical mediator of allergic airway disease, induced expression of intelectin-1 and -2 as well as MCP-1 and -3. When IL-13-induced intelectin-1 and -2 expression was inhibited by RNA interference, IL-13-induced extracellular signal-regulated kinase 1/2 phosphorylation and MCP-1 and -3 production by MLE12 cells was inhibited. Furthermore, inhibition of intelectin expression by airway transfection with shRNA targeting intelectin-1 and -2 attenuated allergen-induced airway inflammation. We conclude that intelectin, a molecule expressed by airway epithelial cells and upregulated in asthma, is required for IL-13-induced MCP-1 and -3 production in mouse lung epithelial cells and contributes to allergic airway inflammation.
authors: Division of Respiratory Diseases, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Naibing
authors: N
authors: Gu
authors: Guannan
authors: G
authors: Kang
authors: Chang'E
authors: C
authors: Jin
authors: Yongjian
authors: Y
authors: Xu
authors: Zhenxiang
authors: Z
authors: Zhang
authors: David J
authors: DJ
authors: Erle
authors: Guohua
authors: G
authors: Zhen
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D054410:Chemokine CCL7 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D006967:Hypersensitivity / Q000150:complications* / Q000201:enzymology; D018793:Interleukin-13 / Q000494:pharmacology*; D007700:Kinetics; D037102:Lectins / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048053:Mitogen-Activated Protein Kinase 6 / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000485:Allergens; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D018793:Interleukin-13; C115657:Itlnb protein, mouse; D037102:Lectins; D010047:Ovalbumin; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6