Impact of a Met(11)Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model.
The surfactant-associated proteins SP-A and D are pattern recognition molecules with collectin structure. A single nucleotide polymorphism (SNP) exchanging a methionine (Met) for a threonine (Thr) in the amino-terminal SP-D domain influences the oligomeric structure and function of the protein. In this study, we investigated the susceptibility of mice transgenic for the human SP-D Met(11)Thr SNP to allergic airway inflammation and consequences for microRNA (miRNA, miR) expression. Mice expressing either human Met or Thr SP-D were sensitized and challenged with ovalbumin (OVA) in an acute model of allergic asthma. The influence of the SP-D polymorphism on the allergic airway inflammation was evaluated by lung function measurement, pulmonary inflammation parameters, morphological analysis and miRNA expression. Airway hyperresponsiveness, allergic inflammation, and mucus metaplasia were not significantly different between mice expressing one or the other allelic variant of SP-D. OVA sensitization and challenge led to significant airway hyperresponsiveness in wildtype mice and significantly lower eosinophil numbers and interleukin 5 levels in Thr SP-D mice. OVA challenge induced an upregulation of miR-21 and 155 in Thr SP-D mice and a downregulation of miR-21 in Met SP-D mice. Our results show that murine expression of human polymorphic SP-D variants does not significantly influence the severity of allergic airway inflammation. MiR-21 and 155 are differentially regulated in transgenic mice in response to allergic inflammation. Further studies are required to elucidate the impact of this SNP on inflammatory conditions of the lung.
1Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
Carla
C
Winkler
Olaf
O
Bahlmann
Janika
J
Viereck
Lars
L
Knudsen
Dirk
D
Wedekind
Heinz Gerd
HG
Hoymann
Jens
J
Madsen
Thomas
T
Thum
Jens M
JM
Hohlfeld
Matthias
M
Ochs
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics*; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism
C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D037663:Pulmonary Surfactant-Associated Protein D; D010047:Ovalbumin