PMID- 24312098
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20131206
LR  - 20211021
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 4
DP  - 2013
TI  - The Interleukin-1alpha Precursor is Biologically Active and is Likely a Key Alarmin 
      in the IL-1 Family of Cytokines.
PG  - 391
LID - 10.3389/fimmu.2013.00391 [doi]
LID - 391
AB  - Among the 11 members of the IL-1 family cytokines, the precursors of IL-1alpha, 
      IL-1beta, and IL-33 have relatively long N-terminal pro-sequences of approximately 
      100 amino acid residues prior to the N-terminus of the mature forms. Compared to 
      the mature forms secreted from the cell, 80-90% of the primary translation 
      product is in the intracellular compartment in the precursor form. However, the 
      precursors are readily released from cells during infections but also with 
      non-infectious conditions such a hypoxia and trauma. In this setting, the 
      precursors act rapidly as "alarmins" in the absence of a processing mechanism to 
      remove the pro-sequence and generate a mature form. In the case of IL-1alpha, the 
      release of the precursor activates adjacent cells via receptor-mediated 
      signaling. However, there are no data comparing the specific activity of the 
      IL-1alpha precursor to the mature form. In the present study, we compared the 
      precursor and mature forms of recombinant human IL-1alpha, IL-1beta, and IL-33 proteins 
      on the induction of cytokines from A549 cells as well as from human peripheral 
      blood mononuclear cells (PBMC). Similar to the mature form, the IL-1alpha precursor 
      was active in inducing IL-6 and TNFalpha, whereas the precursor forms of IL-1beta and 
      IL-33 were not active. On PBMC, precursor and mature IL-1alpha at 0.04 and 0.2 nM 
      were equally active in inducing IL-6. Given the fact that during necrotic cell 
      death, the IL-1alpha precursor is released intact and triggers IL-1 receptors on 
      tissue macrophages, these data identify the precursor form of IL-1alpha as a key 
      player in sterile inflammation.
FAU - Kim, Busun
AU  - Kim B
AD  - Department of Medicine, University of Colorado Denver , Aurora, CO , USA.
FAU - Lee, Youngmin
AU  - Lee Y
FAU - Kim, Eunsom
AU  - Kim E
FAU - Kwak, Areum
AU  - Kwak A
FAU - Ryoo, Soyoon
AU  - Ryoo S
FAU - Bae, Seung Hyeon
AU  - Bae SH
FAU - Azam, Tania
AU  - Azam T
FAU - Kim, Soohyun
AU  - Kim S
FAU - Dinarello, Charles A
AU  - Dinarello CA
LA  - eng
GR  - R01 AI015614/AI/NIAID NIH HHS/United States
GR  - R01 AR045584/AR/NIAMS NIH HHS/United States
GR  - R56 AI015614/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20131120
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC3834611
OTO - NOTNLM
OT  - DAMPs
OT  - IL-1 family cytokine
OT  - precursor IL-1alpha
OT  - recombinant protein
OT  - sterile inflammation
EDAT- 2013/12/07 06:00
MHDA- 2013/12/07 06:01
PMCR- 2013/01/01
CRDT- 2013/12/07 06:00
PHST- 2013/09/08 00:00 [received]
PHST- 2013/11/07 00:00 [accepted]
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2013/12/07 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2013.00391 [doi]
PST - epublish
SO  - Front Immunol. 2013 Nov 20;4:391. doi: 10.3389/fimmu.2013.00391. eCollection 
      2013.