Regulation and function of the caspase-1 in an inflammatory microenvironment

The inflammasome is a complex of proteins that plays a critical role in mounting an inflammatory response in reply to a harmful stimulus that compromises the homeostatic state of the tissue. The NLRP3 inflammasome, which is found in a wound-like environment, is comprised of three components: the NLRP3, the adaptor protein ASC and caspase-1. Interestingly, while 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 find that in an inflammatory microenvironment, caspase-1 is regulated by NFκB. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound-healing caused by the abrogation of NFκB activation. Surprisingly, not only does inhibition of the NFκB/caspase-1 axis disrupt the inflammatory phase of the wound-healing program, 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.

• Publication year

  2015

• Venue

  Journal of Investigative Dermatology

• Publication date

  2015-03-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/jid.2015.119PMID 25815426PMCID 4504759
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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