PMID- 23268368
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20130808
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 72
IP  - 9
DP  - 2013 Sep 1
TI  - The novel cytokine interleukin-36alpha is expressed in psoriatic and rheumatoid 
      arthritis synovium.
PG  - 1569-74
LID - 10.1136/annrheumdis-2012-202264 [doi]
AB  - BACKGROUND: Interleukin (IL)-36alpha is a recently described member of the IL-1 
      cytokine family with pro-inflammatory and clearly pathogenic properties in 
      psoriasis. OBJECTIVE: To determine the IL-36alpha expression in psoriatic arthritis 
      (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: 
      Synovial tissues obtained from arthritis patients were stained for IL-36alpha, IL-36 
      receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and 
      immunofluorescence. Lysates were examined for IL-36alpha by western blot analysis. 
      Synovial fibroblasts (FLS) cultured in the presence of IL-36alpha were assayed for 
      cytokine expression by quantitative real time PCR and multiplex assay. 
      IL-36alpha-induced signal transduction in FLS was analysed by immunoblotting. 
      RESULTS: Expression of IL-36R and its ligands IL-36alpha and IL-36Ra was detected in 
      the synovial lining layer and cellular infiltrates of patients with inflammatory 
      arthritis. IL-36alpha was expressed significantly higher in PsA and RA than in OA 
      synovium. CD138-positive plasma cells were identified as the main cellular source 
      of IL-36alpha. No differences were observed for the expression of IL-36R and IL-36Ra 
      between PsA, RA and OA. Functionally, IL-36alpha induced the expression of IL-6 and 
      IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36alpha is up-regulated in 
      PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 
      production by synovial fibroblasts. Hence, IL-36alpha links plasma cells to 
      inflammatory cytokine production by FLS and may represent a key link between 
      autoimmunity and the induction of synovitis.
FAU - Frey, Silke
AU  - Frey S
AD  - Department of Internal Medicine 3 and Institute for Clinical Immunology, 
      University Hospital of Erlangen-Nuremberg, Erlangen, Germany.
FAU - Derer, Anja
AU  - Derer A
FAU - Messbacher, Maria-Elena
AU  - Messbacher ME
FAU - Baeten, Dominique L P
AU  - Baeten DL
FAU - Bugatti, Serena
AU  - Bugatti S
FAU - Montecucco, Carlomaurizio
AU  - Montecucco C
FAU - Schett, Georg
AU  - Schett G
FAU - Hueber, Axel J
AU  - Hueber AJ
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20121225
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (IL36A protein, human)
RN  - 0 (Interleukin-1)
SB  - IM
MH  - Aged
MH  - Arthritis, Psoriatic/*metabolism/pathology
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - Female
MH  - Humans
MH  - Interleukin-1/*metabolism
MH  - Knee Joint/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*metabolism/pathology
MH  - Synovial Membrane/*metabolism
OTO - NOTNLM
OT  - Arthritis
OT  - Cytokines
OT  - Inflammation
EDAT- 2012/12/27 06:00
MHDA- 2013/10/18 06:00
CRDT- 2012/12/27 06:00
PHST- 2012/12/27 06:00 [entrez]
PHST- 2012/12/27 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
AID - annrheumdis-2012-202264 [pii]
AID - 10.1136/annrheumdis-2012-202264 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2013 Sep 1;72(9):1569-74. doi: 10.1136/annrheumdis-2012-202264. 
      Epub 2012 Dec 25.