PMID- 21454686
OWN - NLM
STAT- MEDLINE
DCOM- 20110801
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 22
DP  - 2011 Jun 3
TI  - Identification of constitutively active interleukin 33 (IL-33) splice variant.
PG  - 20078-86
LID - 10.1074/jbc.M111.219089 [doi]
AB  - IL-33/IL-1F11 is a new member of the IL-1 family ligand and provokes T 
      helper-type immune responses. IL-33 is the ligand of ST2 and IL-1 receptor 
      accessory protein (IL-1RAcP) that triggers nuclear factor-kappa light chain enhancer 
      of activated B cells (NF-kappaB) and MAPK signaling. We discovered a novel short 
      splice variant of IL-33 that was termed spIL-33. The new spIL-33 lacks exon 3 
      containing a proposed caspase-1 cleavage site. We isolated spIL-33 cDNA from the 
      Huh7 human hepatocarcinoma cell line and expressed the recombinant spIL-33 
      protein in Escherichia coli. The recombinant spIL-33 and pro-IL-33 were not 
      cleaved by caspase-1, unlike IL-18 (IL-1F4). The recombinant spIL-33 was 
      constitutively active, and spIL-33-induced inflammatory cytokine production was 
      caspase-1-independent in HMC-1 and Raw 264.7 cells. The recombinant spIL-33 
      induced the phosphorylation of IL-1 receptor-associated kinase (IRAK1), NF-kappaB, 
      p38 MAPK, p44/42 MAPK, and JNK in a time- and dose-dependent manner. Anti-ST2 
      monoclonal antibody specifically blocked the spIL-33-induced cytokine production. 
      In this study, we identified and characterized a new IL-33 splice variant, which 
      was a constitutively active IL-33 isoform. The existence of constitutively active 
      spIL-33 suggests that the biological activity of IL-33 could be triggered by 
      diverse stimulations during immune responses. Further investigation of the 
      spIL-33 expression pattern may contribute to understanding the involvement of 
      IL-33 in inflammatory disorders.
FAU - Hong, Jaewoo
AU  - Hong J
AD  - Laboratory of Cytokine Immunology, Medical Immunology Center, Konkuk University, 
      Seoul, Korea.
FAU - Bae, Suyoung
AU  - Bae S
FAU - Jhun, Hyunjhung
AU  - Jhun H
FAU - Lee, Siyoung
AU  - Lee S
FAU - Choi, Jida
AU  - Choi J
FAU - Kang, Taebong
AU  - Kang T
FAU - Kwak, Areum
AU  - Kwak A
FAU - Hong, Kwangwon
AU  - Hong K
FAU - Kim, Eunsom
AU  - Kim E
FAU - Jo, Seunghyun
AU  - Jo S
FAU - Kim, Soohyun
AU  - Kim S
LA  - eng
SI  - GENBANK/HQ641439
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110322
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (IL33 protein, human)
RN  - 0 (Il33 protein, mouse)
RN  - 0 (Interleukin-33)
RN  - 0 (Interleukins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Protein Precursors)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.1 (IRAK1 protein, human)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 2.7.11.1 (Irak1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Alternative Splicing/*physiology
MH  - Animals
MH  - Base Sequence
MH  - Humans
MH  - Inflammation/genetics/metabolism
MH  - Interleukin-1 Receptor-Associated Kinases/genetics/metabolism
MH  - Interleukin-33
MH  - Interleukins/*biosynthesis/genetics
MH  - Jurkat Cells
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation/physiology
MH  - Protein Isoforms/biosynthesis/genetics
MH  - Protein Precursors/*biosynthesis/genetics
MH  - Rats
MH  - Recombinant Proteins/biosynthesis/genetics
MH  - U937 Cells
PMC - PMC3103380
EDAT- 2011/04/02 06:00
MHDA- 2011/08/02 06:00
PMCR- 2012/06/03
CRDT- 2011/04/02 06:00
PHST- 2011/04/02 06:00 [entrez]
PHST- 2011/04/02 06:00 [pubmed]
PHST- 2011/08/02 06:00 [medline]
PHST- 2012/06/03 00:00 [pmc-release]
AID - S0021-9258(20)51079-X [pii]
AID - M111.219089 [pii]
AID - 10.1074/jbc.M111.219089 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jun 3;286(22):20078-86. doi: 10.1074/jbc.M111.219089. Epub 2011 
      Mar 22.