Makoto Kudo, MD, PhD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Dean Sheppard, MD
,
Lung Biology Center, University of California, San Francisco, CA
Ushio Ryota, MD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Masaki Yamamoto, MD, PhD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Masaharu Shinkai, MD, PhD
,
Respiratory Center, Yokohama City University, Yokohama, Japan
Takeshi Kaneko, MD, PhD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Takashi Sato, MD, PhD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Keisuke Wananabe, MD, PhD
,
Respiratory Center, Yokohama City University, Yokohama, Japan
Nobuyuki Horita, MD, PhD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Kentaro Nakashima, MD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Yusuke Moriyama, MD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Makoto Masuda, MD
,
Respiratory Disease, Yokohama City University, Yokohama, Japan
Rationale: Asthma is characterized by exaggerated airway smooth muscle contractility. IL-17A is widely known to play an important role in asthma, inducing airway inflammation. But it is unclear that the cytokine affect on the airway smooth muscle, which is the major cause of symptoms in the disease.
We investigate how IL-17A affect on airway smooth muscle contractility.
Methods: We made conditional knock out mice (integrin beta8 on dendritic cells). Racking of the integrin mouse fails to induce Th17 cells from abTcells. Then, we checked airway inflammation and airway reactivity after OVA challenge. And we also investigate smooth muscle contraction with or without IL-17A incubation.
Results: Knockout mouse had smaller hyperreactivity than that of wild type mouse. But evaluation of airway inflammation in both mouse were similar.
From muscle bath assay, IL-17A exaggerated smooth muscle contraction in 1 to 12hrs incubation with IL-17A.
In late phase, RhoA and ROCK2 protein expressions were elevated. On the other hand, in early phase RhoA and ROCK2 protein did not increase. But RhoA activation was occurred, in connection with PKC activation.
Conclusions: These results suggest that IL-17A directly exaggerates airway smooth muscle contractility. IL-17A induces RhoA and ROCK2 protein expression through NF-kB pathway. And the cytokine acutely activates RhoA through a PKC-alpha dependent pathway. We also speculated that IL-17A might activate RhoA by activating PKC-alpha and p115RhoGEF.
