PMID- 19717513
OWN - NLM
STAT- MEDLINE
DCOM- 20090923
LR  - 20131121
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 6
DP  - 2009 Sep 15
TI  - Externalization of the leaderless cytokine IL-1F6 occurs in response to 
      lipopolysaccharide/ATP activation of transduced bone marrow macrophages.
PG  - 4021-30
LID - 10.4049/jimmunol.0803301 [doi]
AB  - An interesting trait shared by many members of the IL-1 cytokine family is the 
      absence of a signal sequence that can direct the newly synthesized polypeptides 
      to the endoplasmic reticulum. As a result, these cytokines accumulate 
      intracellularly. Recent studies investigating IL-1beta export established that 
      its release is facilitated via activation of an intracellular multiprotein 
      complex termed the inflammasome. The purpose of the current study was to explore 
      the mechanism by which murine IL-1F6 is released from bone marrow-derived 
      macrophages (BMDMs) and to compare this mechanism to that used by IL-1beta. BMDMs 
      were engineered to overexpress IL-1F6 by retroviral transduction; cells 
      overexpressing GFP also were generated to provide a noncytokine comparator. The 
      transduced cells constitutively expressed IL-1F6 and GFP, but they did not 
      constitutively release these polypeptides to the medium. Enhanced release of 
      IL-1F6 was achieved by treating with LPS followed by ATP-induced activation of 
      the P2X(7) receptor; GFP also was released under these conditions. No obvious 
      proteolytic cleavage of IL-1F6 was noted following P2X(7) receptor-induced 
      release. Stimulus-induced release of IL-1F6 and GFP demonstrated comparable 
      susceptibility to pharmacological modulation. Therefore, transduced IL-1F6 is 
      released in parallel with endogenous mature IL-1beta from LPS/ATP-treated BMDMs, 
      but this externalization process is not selective for cytokines as a noncytokine 
      (GFP) shows similar behavior. These findings suggest that IL-1F6 can be 
      externalized via a stimulus-coupled mechanism comparable to that used by 
      IL-1beta, and they provide additional insight into the complex cellular processes 
      controlling posttranslational processing of the IL-1 cytokine family.
FAU - Martin, Unja
AU  - Martin U
AD  - Department of Inflammation, Amgen, Seattle, WA 98119, USA.
FAU - Scholler, John
AU  - Scholler J
FAU - Gurgel, Jesse
AU  - Gurgel J
FAU - Renshaw, Blair
AU  - Renshaw B
FAU - Sims, John E
AU  - Sims JE
FAU - Gabel, Christopher A
AU  - Gabel CA
LA  - eng
PT  - Journal Article
DEP - 20090828
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (P2rx7 protein, mouse)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 0 (interleukin 1F6, mouse)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/*pharmacology
MH  - Animals
MH  - Bone Marrow Cells
MH  - Interleukin-1/genetics/*metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Transport/drug effects
MH  - Receptors, Purinergic P2/metabolism
MH  - Receptors, Purinergic P2X7
MH  - Transduction, Genetic
EDAT- 2009/09/01 06:00
MHDA- 2009/09/24 06:00
CRDT- 2009/09/01 09:00
PHST- 2009/09/01 09:00 [entrez]
PHST- 2009/09/01 06:00 [pubmed]
PHST- 2009/09/24 06:00 [medline]
AID - jimmunol.0803301 [pii]
AID - 10.4049/jimmunol.0803301 [doi]
PST - ppublish
SO  - J Immunol. 2009 Sep 15;183(6):4021-30. doi: 10.4049/jimmunol.0803301. Epub 2009 
      Aug 28.