PMID- 11562425
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20210715
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 60
IP  - 4
DP  - 2001 Oct
TI  - Tumor necrosis factor receptor (TNFR) 1, but not TNFR2, mediates tumor necrosis 
      factor-alpha-induced interleukin-6 and RANTES in human airway smooth muscle 
      cells: role of p38 and p42/44 mitogen-activated protein kinases.
PG  - 646-55
AB  - Little information is available regarding the mechanisms involved in 
      cytokine-induced synthetic function of human airway smooth muscle (ASM) cells. 
      Here, we report that tumor necrosis factor receptor (TNFR) 1-induced p38 and 
      p42/44 mitogen-activated protein kinase (MAPK) activation modulates tumor 
      necrosis factor-alpha (TNF alpha)-mediated synthetic responses: expression of 
      intercellular adhesion molecule-1 (ICAM-1) and secretion of interleukin (IL)-6 
      and the regulated-on-activation, normal T-cell expressed and secreted (RANTES) 
      chemokine in human ASM cells. Pretreatment of ASM cells with SB203580, a p38 MAPK 
      inhibitor, slightly enhanced TNF alpha-induced ICAM-1 expression in a 
      dose-dependent manner but partially inhibited secretion of RANTES and IL-6. In 
      contrast, PD98059, a p42/44 inhibitor, reduced ICAM-1 expression by 50% but had 
      no effect on TNF alpha-induced RANTES or IL-6 secretion. SB203580 and PD98059 had 
      little effect on TNF alpha-induced nuclear factor-kappa B (NF-kappa B) activation 
      as determined in cells transfected with a NF-kappa B-luciferase reporter 
      construct. We also found that agonistic antibodies specific for either TNFR1 or 
      TNFR2 stimulated IL-6 and RANTES secretion and activated p38 and p42/44 MAPKs. In 
      addition, both antibodies induced NF-kappa B-mediated gene transcription. Using 
      receptor-specific blocking antibodies, we found that TNFR1 primarily regulates 
      TNF alpha-induced IL-6 and RANTES secretion and activation of p38 and p42/44 MAPK 
      pathways. Interestingly, we found that TNFR1 and TNFR2 are expressed differently 
      on the cell surface of ASM cells. Our data suggest that despite the presence of 
      functional TNFR2, TNFR1 associated with MAPK-dependent and -independent pathways 
      is the primary signaling pathway involved in TNF alpha-induced synthetic 
      functions in ASM cells.
FAU - Amrani, Y
AU  - Amrani Y
AD  - Department of Medicine, Pulmonary, Allergy, and Critical Care Division, 
      University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6160, 
      USA. amrani@mail.med.upenn.edu
FAU - Ammit, A J
AU  - Ammit AJ
FAU - Panettieri, R A Jr
AU  - Panettieri RA Jr
LA  - eng
GR  - R01 HL055301/HL/NHLBI NIH HHS/United States
GR  - R01 HL064063/HL/NHLBI NIH HHS/United States
GR  - R01-HL55301/HL/NHLBI NIH HHS/United States
GR  - R01-HL64063/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antigens, CD)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-6)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Bronchi/cytology/enzymology
MH  - Cells, Cultured
MH  - Chemokine CCL5/*metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-6/*metabolism
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Muscle, Smooth/enzymology/*metabolism
MH  - Pyridines/pharmacology
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Receptors, Tumor Necrosis Factor, Type II
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2001/09/20 10:00
MHDA- 2001/10/05 10:01
CRDT- 2001/09/20 10:00
PHST- 2001/09/20 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/09/20 10:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 2001 Oct;60(4):646-55.