Inflammation-induced airway smooth muscle responsiveness is strain dependent in mice.
Different mouse strains display different degrees of inflammation-induced airway hyperresponsiveness in vivo. 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 per se. The differences do not appear to be due to differential expression of TLR or common inflammatory transduction and repressor proteins.
Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Jesper
J
Säfholm
Cecilia
C
Lövdahl
Linda
L
Swedin
Piet J M
PJ
Boels
Sven-Erik
SE
Dahlén
Anders
A
Arner
Mikael
M
Adner
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D013045:Species Specificity; D051193:Toll-Like Receptors / Q000502:physiology; D014132:Trachea / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D002217:Carbachol; D001920:Bradykinin