Cell death in chronic inflammation: breaking the cycle to treat rheumatic disease.
Nat Rev Rheumatol
; 16(9): 496-513, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-32641743
ABSTRACT
Cell death is a vital process that occurs in billions of cells in the human body every day. This process helps maintain tissue homeostasis, supports recovery from acute injury, deals with infection and regulates immunity. Cell death can also provoke inflammatory responses, and lytic forms of cell death can incite inflammation. Loss of cell membrane integrity leads to the uncontrolled release of damage-associated molecular patterns (DAMPs), which are normally sequestered inside cells. Such DAMPs increase local inflammation and promote the production of cytokines and chemokines that modulate the innate immune response. Cell death can be both a consequence and a cause of inflammation, which can be difficult to distinguish in chronic diseases. Despite this caveat, excessive or poorly regulated cell death is increasingly recognized as a contributor to chronic inflammation in rheumatic disease and other inflammatory conditions. Drugs that inhibit cell death could, therefore, be used therapeutically for the treatment of these diseases, and programmes to develop such inhibitors are already underway. In this Review, we outline pathways for the major cell death programmes (apoptosis, necroptosis, pyroptosis and NETosis) and their potential roles in chronic inflammation. We also discuss current and developing therapies that target the cell death machinery.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rheumatic Diseases
/
Cell Death
/
Alarmins
/
Homeostasis
/
Inflammation
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Rev Rheumatol
Journal subject:
REUMATOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
Australia