| First Author | Lee DJ | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 8 | Pages | 2012-2020 |
| PubMed ID | 25815426 | Mgi Jnum | J:222974 |
| Mgi Id | MGI:5646097 | Doi | 10.1038/jid.2015.119 |
| Citation | Lee DJ, et al. (2015) Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment. J Invest Dermatol 135(8):2012-20 |
| abstractText | 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 inflammasome, 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-kappaB. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound healing caused by the abrogation of NF-kappaB activation. Surprisingly, not only does inhibition of the NF-kappaB/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. |
