Abstract
Inflammation is initiated by innate immune cell activation after contact with pathogens or tissue injury. An increasing number of observations have suggested that cellular stress, in the absence of infection or evident damage, can also induce inflammation. Thus, inflammation can be triggered by exogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) - so-called classic inflammation - or by endogenous stress resulting from tissue or cellular dysfunction. External triggers and cellular stress activate the same molecular pathways, possibly explaining why classic and stress-induced inflammation have similar clinical manifestations. In some systemic autoinflammatory diseases (SAIDs), inflammatory cells exhibit reduction-oxidation (redox) distress, having high levels of reactive oxygen species (ROS), which promote proinflammatory cytokine production and contribute to the subversion of mechanisms that self-limit inflammation. Thus, SAIDs can be viewed as a paradigm of stress-related inflammation, being characterized by recurrent flares or chronic inflammation (with no recognizable external triggers) and by a failure to downmodulate this inflammation. Here, we review SAID pathophysiology, focusing on the major cytokines and DAMPs, and on the key roles of redox distress. New therapeutic opportunities to tackle SAIDs by blocking stress-induced pathways and control the response to stress in patients are also discussed.
| Original language | English |
|---|---|
| Pages (from-to) | 670-680 |
| Number of pages | 11 |
| Journal | Nature Reviews Rheumatology |
| Volume | 11 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2015 |
Fingerprint
ASJC Scopus subject areas
- Rheumatology
Cite this
Redox distress and genetic defects conspire in systemic autoinflammatory diseases. / Varga, Georg; Gattorno, Marco; Foell, Dirk; Rubartelli, Anna.
In: Nature Reviews Rheumatology, Vol. 11, No. 11, 01.11.2015, p. 670-680.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Redox distress and genetic defects conspire in systemic autoinflammatory diseases
AU - Varga, Georg
AU - Gattorno, Marco
AU - Foell, Dirk
AU - Rubartelli, Anna
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Inflammation is initiated by innate immune cell activation after contact with pathogens or tissue injury. An increasing number of observations have suggested that cellular stress, in the absence of infection or evident damage, can also induce inflammation. Thus, inflammation can be triggered by exogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) - so-called classic inflammation - or by endogenous stress resulting from tissue or cellular dysfunction. External triggers and cellular stress activate the same molecular pathways, possibly explaining why classic and stress-induced inflammation have similar clinical manifestations. In some systemic autoinflammatory diseases (SAIDs), inflammatory cells exhibit reduction-oxidation (redox) distress, having high levels of reactive oxygen species (ROS), which promote proinflammatory cytokine production and contribute to the subversion of mechanisms that self-limit inflammation. Thus, SAIDs can be viewed as a paradigm of stress-related inflammation, being characterized by recurrent flares or chronic inflammation (with no recognizable external triggers) and by a failure to downmodulate this inflammation. Here, we review SAID pathophysiology, focusing on the major cytokines and DAMPs, and on the key roles of redox distress. New therapeutic opportunities to tackle SAIDs by blocking stress-induced pathways and control the response to stress in patients are also discussed.
AB - Inflammation is initiated by innate immune cell activation after contact with pathogens or tissue injury. An increasing number of observations have suggested that cellular stress, in the absence of infection or evident damage, can also induce inflammation. Thus, inflammation can be triggered by exogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) - so-called classic inflammation - or by endogenous stress resulting from tissue or cellular dysfunction. External triggers and cellular stress activate the same molecular pathways, possibly explaining why classic and stress-induced inflammation have similar clinical manifestations. In some systemic autoinflammatory diseases (SAIDs), inflammatory cells exhibit reduction-oxidation (redox) distress, having high levels of reactive oxygen species (ROS), which promote proinflammatory cytokine production and contribute to the subversion of mechanisms that self-limit inflammation. Thus, SAIDs can be viewed as a paradigm of stress-related inflammation, being characterized by recurrent flares or chronic inflammation (with no recognizable external triggers) and by a failure to downmodulate this inflammation. Here, we review SAID pathophysiology, focusing on the major cytokines and DAMPs, and on the key roles of redox distress. New therapeutic opportunities to tackle SAIDs by blocking stress-induced pathways and control the response to stress in patients are also discussed.
UR - http://www.scopus.com/inward/record.url?scp=84946483485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946483485&partnerID=8YFLogxK
U2 - 10.1038/nrrheum.2015.105
DO - 10.1038/nrrheum.2015.105
M3 - Article
C2 - 26241183
AN - SCOPUS:84946483485
VL - 11
SP - 670
EP - 680
JO - Nature reviews. Rheumatology
JF - Nature reviews. Rheumatology
SN - 1759-4790
IS - 11
ER -