IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma.
Asthma is a heterogeneous disease characterized by airway inflammation and hyperreactivity. IL-17 receptor A (IL-17RA) is a shared receptor subunit required for activity of IL-17 family cytokines, including IL-17A and IL-25. IL-17A and IL-25 induce different proinflammatory responses, and concentrations are elevated in subjects with asthma. However, the individual contributions of IL-17A and IL-25 to disease pathogenesis are unclear. We explored proinflammatory activities of the IL-17 pathway in models of pulmonary inflammation and assessed its effects on contractility of human bronchial airway smooth muscle. In two mouse models, IL-17RA, IL-17RB, or IL-25 blockade reduced airway inflammation and airway hyperreactivity. Individually, IL-17A and IL-25 enhanced contractility of human bronchial smooth muscle induced by methacholine or carbachol. IL-17A had more pronounced effects on methacholine-induced contractility in bronchial rings from donors with asthma compared with donors without asthma. Blocking the IL-17 pathway via IL-17RA may be a useful therapy for some patients with asthma by reducing pulmonary inflammation and airway hyperreactivity.
1 Inflammation Research, and.
Cynthia R
CR
Willis
1 Inflammation Research, and.
Lori
L
Siegel
1 Inflammation Research, and.
Anh
A
Leith
1 Inflammation Research, and.
Deanna
D
Mohn
1 Inflammation Research, and.
Sabine
S
Escobar
1 Inflammation Research, and.
Sharon
S
Wannberg
2 Genome Analysis Unit, Amgen Inc., Seattle, Washington.
Kira
K
Misura
1 Inflammation Research, and.
Erika
E
Rickel
3 Comparative Biology and Safety Sciences, Amgen Inc., Cambridge, Massachusetts; and.
James B
JB
Rottman
1 Inflammation Research, and.
Michael R
MR
Comeau
1 Inflammation Research, and.
John K
JK
Sullivan
1 Inflammation Research, and.
Daniela P
DP
Metz
4 Janssen Research and Development LLC, Spring House, Pennsylvania.
Joel
J
Tocker
1 Inflammation Research, and.
Alison L
AL
Budelsky
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000502:physiology*; D015398:Signal Transduction
C491673:Il17ra protein, mouse; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse; D053722:Receptors, Interleukin-17
IL-17A; IL-17RA; IL-25; asthma; bronchial hyperreactivity