| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2015: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
|
|---|
| Outline of Final Research Achievements |
It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce CGRP. This induction of CGRP is independent of Bcl-10 or Malt-1 but dependent on TRPV1/TRPA1 ion channels. Hind paw β-glucan injection after Nav1.8-positive nociceptor ablation or in TRPV1/TRPA1 deficiency showed dramatically increased osteo-inflammation accompanied by impaired CGRP production. Strikingly, CGRP suppressed β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of NF-κB p65 by the transcriptional repressor Jdp2 and inhibition of actin polymerization, respectively. These findings clearly suggest the role of Dectin-1-mediated sensocrine pathways in the resolution of fungal osteo-inflammation.
|
