Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 135, Issue 8, Pages 2012-2020Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2015.119
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Funding
- Hellman Faculty Fellowship
- NIH/NIAMS [5R01AR053185-03]
- American Cancer Society [115457-RSG-08-164-01-DDC]
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The inflammasome is a complex of proteins that has a critical role in mounting an inflammatory response in reply to a harmful stimulus that compromises the homeostatic state of the tissue. The NLRP3 inflammasonne, which is found in a wound-like environment, is comprised of three components: the NLRP3, the adaptor protein ASC and caspase-1. Interestingly, although ASC levels do not fluctuate, caspase-1 levels are elevated in both physiological and pathological conditions. Despite the observation that merely raising caspase-1 levels is sufficient to induce inflammation, the crucial question regarding the mechanism governing its expression is unexplored. We found that, in an inflammatory microenvironment, caspase-1 is regulated by NF-kappa B. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound healing caused by the abrogation of NF-kappa B activation. Surprisingly, not only does inhibition of the NF-kappa B/caspase-1 axis disrupt the inflammatory phase of the wound-healing program, but it also impairs the stimulation of cutaneous epithelial stem cells of the proliferative phase. These data provide a mechanistic basis for the complex interplay between different phases of the wound-healing response in which the downstream signaling activity of immune cells can kindle the amplification of local stem cells to advance tissue repair.
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