Inflammation-induced airway smooth muscle responsiveness is strain dependent in mice

Jesper Säfholm (1) , Cecilia Lövdahl (2) , Linda Swedin (1) , Piet J.M. Boels (1) , Sven-Erik Dahlén (1) , Anders Arner (2) , Mikael Adner (1)

1 Karolinska Institutet [Stockholm]
2 Division of Genetic Physiology

Different mouse strains display different degrees of inflammation-induced airway hyperresponsiveness . It is not known whether these variations are attributable to distinct properties of the airway smooth muscle. Therefore, tracheal ring segments from C57BL/6 and BALB/c mice were exposed to three different pro-inflammatory stimuli for 4 days while maintained under tissue-culture conditions: tumour necrosis factor α (100 ng/ml), the Toll-like receptor (TLR) 3 agonist polyI:C (10 μg/ml), and the TLR4 agonist LPS (10 μg/ml). The contractile responses to carbachol, 5-hydroxytryptamine (5-HT) and bradykinin were assessed after culture. In addition, gene expression of TLR1-TLR9, pivotal inflammatory signal transduction proteins (jun-kinase, p38 and p65) and critical negative regulators of inflammation (A20, Itch, Tax1bp1 and RNF11) were studied in tracheal smooth muscle strips, fresh and following treatment for 4 days with LPS, from both strains. No differences between the strains were detected regarding the response of freshly isolated preparations to carbachol, 5-HT and bradykinin. After stimulation with pro-inflammatory mediators, contractions in response to 5-HT and bradykinin, but not to carbachol, were up-regulated. This up-regulation was markedly larger in BALB/c than in C57BL/6 segments and depended on the type of inflammatory stimulus. Expression of the genes investigated did not differ between the two strains. These findings indicate that strain differences in airway hyperresponsiveness can be linked to differences in the responsiveness of airway smooth muscle to pro-inflammatory mediators . These differences do not appear to be due to differential expression of TLR or common inflammatory transduction and repressor proteins.

Mots clés: Contractions; strains; Toll-like receptors; trachea

Domaines: Pneumologie et système respiratoire

Jesper Säfholm, Cecilia Lövdahl, Linda Swedin, Piet J.M. Boels, Sven-Erik Dahlén, et al.. Inflammation-induced airway smooth muscle responsiveness is strain dependent in mice. Pulmonary Pharmacology & Therapeutics, 2011, 24 (4), pp.361. ⟨10.1016/j.pupt.2011.01.001⟩. ⟨hal-00753955⟩