PMID- 21913843
OWN - NLM
STAT- MEDLINE
DCOM- 20120116
LR  - 20220409
IS  - 1521-0499 (Electronic)
IS  - 0190-2148 (Print)
IS  - 0190-2148 (Linking)
VI  - 37
IP  - 8
DP  - 2011 Oct
TI  - Interferon-gamma and tumor necrosis factor-alpha act synergistically to up-regulate 
      tissue factor in alveolar epithelial cells.
PG  - 509-17
LID - 10.3109/01902148.2011.605512 [doi]
AB  - Fibrin deposition mediated through activation of tissue factor (TF) in the 
      airspace is central to the pathogenesis of acute lung injury. Defining the 
      mechanisms of TF regulation in the lung is critical to understanding pulmonary 
      fibrin formation. Tumor necrosis factor-alpha (TNF-alpha) up-regulates TF in the injured 
      lung, and there is emerging evidence that another cytokine, interferon-gamma (IFN-gamma), 
      also modulates expression. The effects of TNF-alpha and IFN-gamma on regulation of TF 
      were studied in alveolar epithelial A549 cells. In addition, potential mechanisms 
      of modulation of TF expression by the 2 cytokines were analyzed with the 
      hypothesis that IFN-gamma acts synergistically with TNF-alpha to up-regulate alveolar 
      epithelial TF through modulation of TNF receptor (TNFR) expression. TNF-alpha but not 
      IFN-gamma treatment increased TF mRNA, protein, and cell surface TF activity. The 
      combination of IFN-gamma and TNF-alpha treatment augmented the effects of TNF-alpha on TF 
      up-regulation and also increased release of procoagulant microparticles (MPs) 
      from A549 cells. IFN-gamma modulated expression of both TNF-alpha receptors. Studies 
      utilizing neutralizing antibodies against the two TNF receptors showed that the 
      TF effects were mediated primarily through augmentation of TNFR1-dependent 
      cellular responses. These findings have important implications for regulation of 
      fibrin formation in the lung in the setting of acute inflammation.
FAU - Bastarache, Julie A
AU  - Bastarache JA
AD  - Division of Allergy, Pulmonary and Critical Care Medicine, Department of 
      Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. 
      julie.bastarache@vanderbilt.edu
FAU - Sebag, Sara C
AU  - Sebag SC
FAU - Grove, Brandon S
AU  - Grove BS
FAU - Ware, Lorraine B
AU  - Ware LB
LA  - eng
GR  - HL090785/HL/NHLBI NIH HHS/United States
GR  - HL103836/HL/NHLBI NIH HHS/United States
GR  - T32 HL087738/HL/NHLBI NIH HHS/United States
GR  - HL088263/HL/NHLBI NIH HHS/United States
GR  - R01 HL088263/HL/NHLBI NIH HHS/United States
GR  - K24 HL103836/HL/NHLBI NIH HHS/United States
GR  - K08 HL090785/HL/NHLBI NIH HHS/United States
GR  - 5 K12 HD 043483-05/HD/NICHD NIH HHS/United States
GR  - K12 HD043483/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Exp Lung Res
JT  - Experimental lung research
JID - 8004944
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Alveolar Epithelial Cells/*drug effects/*metabolism
MH  - Cell Line
MH  - Cell-Derived Microparticles/drug effects/metabolism
MH  - Drug Synergism
MH  - Humans
MH  - Interferon-gamma/*administration & dosage
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Thromboplastin/*genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*administration & dosage
MH  - Up-Regulation/drug effects
PMC - PMC3652424
MID - NIHMS457822
COIS- Declaration of interest: The authors report no conflicts of interest.
EDAT- 2011/09/15 06:00
MHDA- 2012/01/17 06:00
PMCR- 2013/05/13
CRDT- 2011/09/15 06:00
PHST- 2011/09/15 06:00 [entrez]
PHST- 2011/09/15 06:00 [pubmed]
PHST- 2012/01/17 06:00 [medline]
PHST- 2013/05/13 00:00 [pmc-release]
AID - 10.3109/01902148.2011.605512 [doi]
PST - ppublish
SO  - Exp Lung Res. 2011 Oct;37(8):509-17. doi: 10.3109/01902148.2011.605512.