PMID- 12149127
OWN - NLM
STAT- MEDLINE
DCOM- 20021204
LR  - 20181130
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 367
IP  - Pt 3
DP  - 2002 Nov 1
TI  - Involvement of phospholipases D1 and D2 in sphingosine 1-phosphate-induced ERK 
      (extracellular-signal-regulated kinase) activation and interleukin-8 secretion in 
      human bronchial epithelial cells.
PG  - 751-60
AB  - Sphingosine 1-phosphate (S1P), a metabolite of sphingomyelin degradation, 
      stimulates interleukin-8 (IL-8) secretion in human bronchial epithelial (Beas-2B) 
      cells. The molecular mechanisms regulating S1P-mediated IL-8 secretion are yet to 
      be completely defined. Here we provide evidence that activation of phospholipases 
      D1 and D2 (PLD1 and PLD2) by S1P regulates the phosphorylation of 
      extracellular-signal-regulated kinase (ERK) and IL-8 secretion in Beas-2B cells. 
      S1P, in a time- and dose-dependent manner, enhanced the threonine/tyrosine 
      phosphorylation of ERK. The inhibition of S1P-induced ERK phosphorylation by 
      pertussis toxin and PD 98059 indicated coupling of S1P receptors to G(i) and the 
      ERK signalling cascade respectively. Treatment of Beas-2B cells with butan-1-ol, 
      but not butan-3-ol, abrogated the S1P-induced phosphorylation of Raf-1 and ERK, 
      suggesting that PLD is involved in this activation. The roles of PLD1 and PLD2 in 
      ERK activation and IL-8 secretion activated by S1P were investigated by infecting 
      cells with adenoviral constructs of wild-type and catalytically inactive mutants 
      of PLD1 and PLD2. Infection of Beas-2B cells with the wild-type constructs 
      resulted in the activation of PLD1 and PLD2 by S1P and PMA. Also, the enhanced 
      production of [(32)P]phosphatidic acid and [(32)P]phosphatidylbutanol in the 
      presence of butan-1-ol and the increased phosphorylation of ERK by S1P were 
      blocked by the catalytically inactive mutants hPLD1-K898R and mPLD2-K758R. 
      Transient transfection of Beas-2B cells with human PLD1 and mouse PLD2 cDNAs 
      potentiated S1P-mediated IL-8 secretion compared with vector controls. In 
      addition, PD 98059 attenuated IL-8 secretion induced by S1P in a dose-dependent 
      fashion. These results demonstrate that both PLD1 and PLD2 participate in S1P 
      stimulation of ERK phosphorylation and IL-8 secretion in bronchial epithelial 
      cells.
FAU - Wang, Lixin
AU  - Wang L
AD  - Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins 
      University, Baltimore, MD 21224, USA.
FAU - Cummings, Rhett
AU  - Cummings R
FAU - Usatyuk, Peter
AU  - Usatyuk P
FAU - Morris, Andrew
AU  - Morris A
FAU - Irani, Kaikobad
AU  - Irani K
FAU - Natarajan, Viswanathan
AU  - Natarajan V
LA  - eng
GR  - HL 47671/HL/NHLBI NIH HHS/United States
GR  - HL 71152/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  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Flavonoids)
RN  - 0 (Interleukin-8)
RN  - 0 (Lysophospholipids)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.4.- (phospholipase D2)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - EC 3.1.4.4 (phospholipase D1)
RN  - NGZ37HRE42 (Sphingosine)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Bronchi/cytology/*drug effects/enzymology/metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Epithelial Cells/drug effects/enzymology/metabolism
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - *Lysophospholipids
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Pertussis Toxin/pharmacology
MH  - Phospholipase D/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-raf/metabolism
MH  - Sphingosine/*analogs & derivatives/*pharmacology
PMC - PMC1222936
EDAT- 2002/08/01 10:00
MHDA- 2002/12/05 04:00
PMCR- 2003/05/01
CRDT- 2002/08/01 10:00
PHST- 2002/07/30 00:00 [accepted]
PHST- 2002/07/29 00:00 [revised]
PHST- 2002/04/12 00:00 [received]
PHST- 2002/08/01 10:00 [pubmed]
PHST- 2002/12/05 04:00 [medline]
PHST- 2002/08/01 10:00 [entrez]
PHST- 2003/05/01 00:00 [pmc-release]
AID - BJ20020586 [pii]
AID - 10.1042/BJ20020586 [doi]
PST - ppublish
SO  - Biochem J. 2002 Nov 1;367(Pt 3):751-60. doi: 10.1042/BJ20020586.