Dysfunctional inflammasome in Schnitzler's syndrome.
OBJECTIVE
IL-1beta plays a key role in the pathogenesis of Schnitzler's syndrome (SS). We have investigated inflammasome activity in peripheral blood mononuclear cells (PBMCs) from a patient affected by a variant type of SS.


METHODS
PBMCs were purified by Ficoll and examined for ability to secrete IL-1beta and -18, expression and function of the P2X(7) receptor and expression of apoptosis-associated speck-like protein containing a caspase recruitment domaine (ASC) and NOD-like receptor protein 3 (NLRP3) before and after the therapy with steroid. Furthermore, extracellular adenosine 5'-triphosphate (ATP) blood levels were determined by luciferase assay. Expression of inflammasome components was measured by real time PCR and western blotting.


RESULTS
PBMCs of patient with SS showed a high, spontaneous and lipopolysaccharide-stimulated, IL-1beta release but low response to stimulation with the P2X(7) agonist benzoyl ATP. P2X(7) expression was several fold increased, whereas ASC expression was dramatically decreased compared with PBMCs from healthy controls. NLRP3 expression was unchanged. Prednisone treatment induced remission of clinical symptoms and normalized IL-1beta secretion and P2X(7) and ASC expression.


CONCLUSIONS
These findings reveal the presence of an overall derangement of the inflammasome and IL-1beta processing and release in SS.
Pizzirani
Cinzia
C
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy.
Falzoni
Simonetta
S
Govoni
Marcello
M
La Corte
Renato
R
Donadei
Simona
S
Di Virgilio
Francesco
F
Trotta
Francesco
F
Lo Monaco
Andrea
A
D000328:Adult; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D046912:Multiprotein Complexes / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000097:blood; D058486:Receptors, Purinergic P2X7; D019873:Schnitzler Syndrome / Q000097:blood*
D018836:Inflammation Mediators; D020382:Interleukin-18; D053583:Interleukin-1beta; D046912:Multiprotein Complexes; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7