TY - JOUR
T1 - Therapeutic strategies in inflammasome mediated diseases of the liver
AU - Hoque, Rafaz
AU - Vodovotz, Yoram
AU - Mehal, Wajahat
N1 - Funding Information:
This work was supported by NIH K08DK092281 (R.H.), VA Merit award and NIH R01DK076674-01A2 (W.Z.M.), and by NIH UO1-DK-072146 (Y.V.).
Funding Information:
The underlying research reported in the study was funded by the NIH Institutes of Health.
PY - 2013/5
Y1 - 2013/5
N2 - Tissue stress and cell death result in inflammation even in the absence of pathogens. Such sterile inflammation is dependent on a cytosolic complex of proteins inside immune cells termed the inflammasome. This complex converts two groups of extracellular signals into an inflammatory response via activation of caspase-1 and secretion of IL-1β and IL-18. Group 1 signals are typically TOLL like receptor agonists and result in transcriptional upregulation of inflammasome components and pro-cytokines. Group 2 signals are diverse, ranging from uric acid to ATP, and lead to assembly and activation of the inflammasome complex. Inflammasome components are required for a wide range of acute and chronic pathologies, including experimental alcoholic and non-alcoholic steatohepatitis, and drug-induced liver injury. Collectively, group 1 and 2 signals, inflammasome components, and cytokine receptors provide a rich source of therapeutic targets. Many of the advances in the field have come from standard reductionist experiments. Progress in the understanding of complex human systems will, however, be dependent on novel strategies such as systems analysis, which analyze large data sets to provide new insights.
AB - Tissue stress and cell death result in inflammation even in the absence of pathogens. Such sterile inflammation is dependent on a cytosolic complex of proteins inside immune cells termed the inflammasome. This complex converts two groups of extracellular signals into an inflammatory response via activation of caspase-1 and secretion of IL-1β and IL-18. Group 1 signals are typically TOLL like receptor agonists and result in transcriptional upregulation of inflammasome components and pro-cytokines. Group 2 signals are diverse, ranging from uric acid to ATP, and lead to assembly and activation of the inflammasome complex. Inflammasome components are required for a wide range of acute and chronic pathologies, including experimental alcoholic and non-alcoholic steatohepatitis, and drug-induced liver injury. Collectively, group 1 and 2 signals, inflammasome components, and cytokine receptors provide a rich source of therapeutic targets. Many of the advances in the field have come from standard reductionist experiments. Progress in the understanding of complex human systems will, however, be dependent on novel strategies such as systems analysis, which analyze large data sets to provide new insights.
UR - http://www.scopus.com/inward/record.url?scp=84876292214&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2012.12.017
DO - 10.1016/j.jhep.2012.12.017
M3 - Comment/debate
AN - SCOPUS:84876292214
SN - 0168-8278
VL - 58
SP - 1047
EP - 1052
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 5
ER -