13.1 Flashcards
IL-1 is produced as ___, an ___ precursor
Pro-IL-1, inactive precursor
What enzyme activates pro-IL-1 and where does it cleave pro-IL-1
IL-1-converting enzyme (ICE) i.e. cryopyrin, i.e. CASPASE-1; cleaves precursor at residue 116
In familial cold urticaria, exposure to cold stimulates ___ due to a mutation
Cryopyrin i.e. caspase-1 i.e. IL-1-converting enzyme, so it stimulates local and systemic signs of acute inflammation!
Caspase-1 is a member of ___-___ ___ family
NOD like receptor family
Activation of NLRs leads to the formation of an ___, also called ___, which leads to activation of caspase-1 and then activation of ___
Inflammasome or apoptosome
Leads to activation of caspase-1 which activates pro-IL-1 to IL-1
Gout is due to excess consumption of ___ rich foods
Purine
In gout, there is formation of ___ ___that exceeds renal clearance capacity, leading to precipitation as crystals in joints
Monosodium urate
Monosodium urate crystals activate ___, and other ___ are also activated by crystals/asbestos, etc.
NLRP3
Other NLRs
Activation of NLRP3 -> activation of caspase 1 -> IL-1!
Anakinra is an ___ receptor ___
IL-1 receptor antagonists.
MAJOR CONTRAINDICATION of anakinra is:
In neutropenia!
Activation of inflammasome formation needs 2 signals:
Signal 1 = priming esp. by TLRs or cytokine receptors
Signal 2 = activation esp. by NLRs (but other things like toxins, bac/vir DNA/RNA, etc.)
After inflammasome activation, the cell dies by ___
Pyroptosis
Flagellin from ___ can activate the inflammasome, by activating ___
Salmonella
NLRC4
When adipocytes die, they release lipid derived molecules like ___ and ___ that form crystals that can activate ___
Palmitate and ceramides
NLRP3 -> activation of inflammasome -> IL-1