| First Author | Kobayashi M | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 2 | Pages | 393-402 |
| PubMed ID | 22105467 | Mgi Jnum | J:179816 |
| Mgi Id | MGI:5304212 | Doi | 10.1002/eji.201141845 |
| Citation | Kobayashi M, et al. (2012) IFN-gamma elevates airway hyper-responsiveness via up-regulation of neurokinin A/neurokinin-2 receptor signaling in a severe asthma model. Eur J Immunol 42(2):393-402 |
| abstractText | The adoptive transfer of OVA-specific Th1 cells into WT mice followed by OVA inhalation induces a significant elevation of airway hyper-responsiveness (AHR) with neutrophilia but not mucus hypersecretion. Here, we demonstrate that the airway inflammation model, pathogenically characterized as severe asthma, was partly mimicked by i.n. administration of IFN-gamma. The administration of IFN-gamma instead of Th1 cells caused AHR elevation but not neutrophilia, and remarkably induced neurokinin-2 receptor (NK2R) expression along with neurokinin A (NKA) production in the lung. To evaluate whether NKA/NK2R was involved in airway inflammation, we first investigated the role of NKA/NK2R-signaling in airway smooth muscle cells (ASMCs) in vitro. NK2R mRNA expression was significantly augmented in tracheal tube-derived ASMCs of WT mice but not STAT-1(-/-) mice after stimulation with IFN-gamma. In addition, methacholine-mediated Ca(2+) influx into the ASMCs was significantly reduced in the presence of NK2R antagonist. Moreover, the NK2R antagonist strongly inhibited IFN-gamma-dependent AHR elevation in vivo. Thus, these results demonstrated that IFN-gamma directly acts on ASMCs to elevate AHR via the NKA/NK2R-signaling cascade. Our present findings suggested that NK2R-mediated neuro-immuno crosstalk would be a promising target for developing novel drugs in Th1-cell-mediated airway inflammation, including severe asthma. |
