title: Secretory leukocyte protease inhibitor plays an important role in the regulation of allergic asthma in mice.
abstract: Secretory leukocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is observed at high levels in asthma patients. Resiquimod, a TLR7/8 ligand, is protective against acute and chronic asthma, and it increases SLPI expression of macrophages in vitro. However, the protective role played by SLPI and the interactions between the SLPI and resiquimod pathways in the immune response occurring in allergic asthma have not been fully elucidated. To evaluate the role of SLPI in the development of asthma phenotypes and the effect of resiquimod treatment on SLPI, we assessed airway resistance and inflammatory parameters in the lungs of OVA-induced asthmatic SLPI transgenic and knockout mice and in mice treated with resiquimod. Compared with wild-type mice, allergic SLPI transgenic mice showed a decrease in lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), and plasma IgE levels (p < 0.001). Allergic SLPI knockout mice displayed phenotype changes significantly more severe compared with wild-type mice. These phenotypes included lung resistance (p < 0.001), airway eosinophilia (p < 0.001), goblet cell hyperplasia (p < 0.001), cytokine levels in the lungs (p < 0.05), and plasma IgE levels (p < 0.001). Treatment of asthmatic transgenic mice with resiquimod increased the expression of SLPI and decreased inflammation in the lungs; resiquimod treatment was still effective in asthmatic SLPI knockout mice. Taken together, our study showed that the expression of SLPI protects against allergic asthma phenotypes, and treatment by resiquimod is independent of SLPI expression, displayed through the use of transgenic and knockout SLPI mice.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec H3A 2T5, Canada.
authors.forename: Rafael
authors.initials: R
authors.lastname: Marino
authors.forename: Thusanth
authors.initials: T
authors.lastname: Thuraisingam
authors.forename: Pierre
authors.initials: P
authors.lastname: Camateros
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kanagaratham
authors.forename: Yong Zhong
authors.initials: YZ
authors.lastname: Xu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Henri
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Yang
authors.forename: Guoan
authors.initials: G
authors.lastname: He
authors.forename: Aihao
authors.initials: A
authors.lastname: Ding
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D000208:Acute Disease; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*
chemical_list: D000485:Allergens; D053481:Secretory Leukocyte Peptidase Inhibitor