title: Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment.
abstract: 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-κB. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound healing caused by the abrogation of NF-κB activation. Surprisingly, not only does inhibition of the NF-κB/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.
authors: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors: Dai-Jen
authors: DJ
authors: Lee
authors: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors: Fei
authors: F
authors: Du
authors: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors: Shih-Wei
authors: SW
authors: Chen
authors: IFOM-inSTEM Joint Research Laboratory, Institute for Stem Cell Biology and Regenerative Medicine, Centre for Inflammation and Tissue Homeostasis, Bangalore, India.
authors: Manando
authors: M
authors: Nakasaki
authors: IFOM-inSTEM Joint Research Laboratory, Institute for Stem Cell Biology and Regenerative Medicine, Centre for Inflammation and Tissue Homeostasis, Bangalore, India.
authors: Isha
authors: I
authors: Rana
authors: Department of Chemistry and Biochemistry, Signaling Systems Laboratory, University of California, San Diego, La Jolla, California, USA.
authors: Vincent F S
authors: VFS
authors: Shih
authors: Department of Chemistry and Biochemistry, Signaling Systems Laboratory, University of California, San Diego, La Jolla, California, USA.
authors: Alexander
authors: A
authors: Hoffmann
authors: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA; IFOM-inSTEM Joint Research Laboratory, Institute for Stem Cell Biology and Regenerative Medicine, Centre for Inflammation and Tissue Homeostasis, Bangalore, India; Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA. Electronic address: colinj@instem.res.in.
authors: Colin
authors: C
authors: Jamora
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000502:physiology*; D053181:Caspase 8 / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000502:physiology*; D003872:Dermatitis / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D006706:Homeostasis / Q000502:physiology; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: D016328:NF-kappa B; D053181:Caspase 8; D020170:Caspase 1