| First Author | Qu J | Year | 2017 |
| Journal | JCI Insight | Volume | 2 |
| Issue | 1 | Pages | e90139 |
| PubMed ID | 28097237 | Mgi Jnum | J:290199 |
| Mgi Id | MGI:6407618 | Doi | 10.1172/jci.insight.90139 |
| Citation | Qu J, et al. (2017) Oxidized CaMKII promotes asthma through the activation of mast cells. JCI Insight 2(1):e90139 |
| abstractText | Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVdelta knockin (MMVVdelta) mice. Compared with WT mice, the allergen-challenged MMVVdelta mice displayed less airway hyperresponsiveness (AHR) and inflammation. These MMVVdelta mice exhibited reduced levels of ROS and diminished recruitment of mast cells to the lungs. OVA-activated bone marrow-derived mast cells (BMMCs) from MMVVdelta mice showed a significant inhibition of ROS and ox-CaMKII expression. ROS generation was dependent on intracellular Ca(2+) concentration in BMMCs. Importantly, OVA-activated MMVVdelta BMMCs had suppressed degranulation, histamine release, leukotriene C4, and IL-13 expression. Adoptive transfer of WT, but not MMVVdelta, BMMCs, reversed the alleviated AHR and inflammation in allergen-challenged MMVVdelta mice. The CaMKII inhibitor KN-93 significantly suppressed IgE-mediated mast cell activation and asthma. These studies support a critical but previously unrecognized role of ox-CaMKII in mast cells that promotes asthma and suggest that therapies to reduce ox-CaMKII may be a novel approach for asthma. |
