PMID- 18776134
OWN - NLM
STAT- MEDLINE
DCOM- 20090305
LR  - 20211020
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 40
IP  - 3
DP  - 2009 Mar
TI  - IL-6 cytoprotection in hyperoxic acute lung injury occurs via suppressor of 
      cytokine signaling-1-induced apoptosis signal-regulating kinase-1 degradation.
PG  - 314-24
LID - 10.1165/rcmb.2007-0287OC [doi]
AB  - Hyperoxic acute lung injury (HALI) is characterized by a cell death response that 
      is inhibited by IL-6. Suppressor of cytokine signaling-1 (SOCS-1) is an 
      antiapoptotic negative regulator of the IL-6-mediated Janus kinase-signal 
      transducer and activator of transcription signaling pathway. We hypothesized that 
      SOCS-1 is a critical regulator and key mediator of IL-6-induced cytoprotection in 
      HALI. To test this hypothesis, we characterized the expression of SOCS-1 and 
      downstream apoptosis signal-regulating kinase (ASK)-1-Jun N-terminal kinase 
      signaling molecules in small airway epithelial cells in the presence of H(2)O(2), 
      which induces oxidative stress. We also examined these molecules in wild-type and 
      lung-specific IL-6 transgenic (Tg(+)) mice exposed to 100% oxygen for 72 hours. 
      In control small airway epithelial cells exposed to H(2)O(2) or in wild-type mice 
      exposed to 100% oxygen, a marked induction of ASK-1 and pJun N-terminal kinase 
      was observed. Both IL-6-stimulated endogenous SOCS-1 and SOCS-1 overexpression 
      abolished H(2)O(2)-induced ASK-1 activation. In addition, IL-6 Tg(+) mice exposed 
      to 100% oxygen exhibited reduced ASK-1 levels and enhanced SOCS-1 expression 
      compared with wild-type mice. Interestingly, no significant changes in activation 
      of the key ASK-1 activator, tumor necrosis factor receptor-1/tumor necrosis 
      factor receptor-associated factor-2 were observed between wild-type and IL-6 
      Tg(+) mice. Furthermore, the interaction between SOCS-1 and ASK-1 promotes 
      ubiquitin-mediated degradation both in vivo and in vitro. These studies 
      demonstrate that SOCS-1 is an important regulator in IL-6-induced cytoprotection 
      against HALI.
FAU - Kolliputi, Narasaiah
AU  - Kolliputi N
AD  - Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General 
      Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch 148, Boston, MA 
      02114, USA.
FAU - Waxman, Aaron B
AU  - Waxman AB
LA  - eng
GR  - R01HL074859/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080905
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Interleukin-6)
RN  - 0 (Oxidants)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (SCGB1A1 protein, human)
RN  - 0 (Scgb1a1 protein, mouse)
RN  - 0 (Socs1 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 1 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (TNF Receptor-Associated Death Domain Protein)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tradd protein, mouse)
RN  - 9060-09-7 (Uteroglobin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
RN  - EC 2.7.11.25 (Map3k5 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Acute Lung Injury/*metabolism/pathology
MH  - Animals
MH  - Caspase 8/genetics/metabolism
MH  - Cells, Cultured
MH  - Cytoprotection/*physiology
MH  - Epithelial Cells/cytology/physiology
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Hyperoxia/*metabolism/pathology
MH  - Interleukin-6/genetics/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - MAP Kinase Kinase Kinase 5/genetics/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Oxidants/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Signal Transduction/physiology
MH  - Suppressor of Cytokine Signaling 1 Protein
MH  - Suppressor of Cytokine Signaling Proteins/genetics/*metabolism
MH  - TNF Receptor-Associated Death Domain Protein/genetics/metabolism
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Uteroglobin/genetics/metabolism
PMC - PMC2645529
EDAT- 2008/09/09 09:00
MHDA- 2009/03/06 09:00
PMCR- 2010/03/01
CRDT- 2008/09/09 09:00
PHST- 2008/09/09 09:00 [pubmed]
PHST- 2009/03/06 09:00 [medline]
PHST- 2008/09/09 09:00 [entrez]
PHST- 2010/03/01 00:00 [pmc-release]
AID - 2007-0287OC [pii]
AID - ajrcmb403314 [pii]
AID - 10.1165/rcmb.2007-0287OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2009 Mar;40(3):314-24. doi: 10.1165/rcmb.2007-0287OC. 
      Epub 2008 Sep 5.