Abstract
The biomolecular mechanisms that mediate signal transduction by type 11 (γ) interferon (IFN) are poorly understood. IFN-γ is a potent growth inhibitory cytokine also endowed with antiviral, immunomodulatory, and differentiating activities on various cell targets, including neural cells. IFN-γ induced a rapid and transient activation of phospholipase A2 in LAN-5, a human neuroblastoma cell line. A consequence of phospholipase A2 activation was the release of arachidonic acid and the generation of lysophospholipids from membrane phospholipids. Treatment of pre-labeled LAN-5 cells with a receptor-saturating concentration of IFN-γ led to a time-dependent release of [3H]arachidonic acid into the culture media and generation or [32P]lysophosphatidylcholine. Pretreatment of cultures with the phospholipase A2 inhibitor, bromophenacyl bromide, markedly inhibited both [3H]arachidonic acid release and lysophosphatidylcholine production induced by IFN-γ treatment. Pretreatment of LAN-5 cells with nordihydroguaiaretic acid, a lipoxygenase inhibitor, or with indomethacin, a cyclooxygenase inhibitor, amplified the release of[3H]arachidonic acid and production of lysophosphatidylcholine induced by non-saturating concentrations of IFN-γ. In parallel, and with the same time-dependent effect, a significant decrease in phosphatidylcholine labeling was observed in IFN-γ-treated cells, further indicating that a potential signal transduction mechanism of IFN-γ is the hydrolysis of membrane phosphatidylcholine by phospholipase A2.
| Original language | English |
|---|---|
| Pages (from-to) | 17-21 |
| Number of pages | 5 |
| Journal | FEBS Letters |
| Volume | 310 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Sep 21 1992 |
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Keywords
- Indomethacin
- Interferon-γ
- Neuroblastoma
- Nordihydroguaiaretic acid (NDGA)
- Phospholipase A
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Stimulation of receptor-coupled phospholipase A2 by interferon-γ. / Ponzoni, Mirco; Montaldo, Paolo G.; Cornaglia-Ferraris, Paolo.
In: FEBS Letters, Vol. 310, No. 1, 21.09.1992, p. 17-21.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stimulation of receptor-coupled phospholipase A2 by interferon-γ
AU - Ponzoni, Mirco
AU - Montaldo, Paolo G.
AU - Cornaglia-Ferraris, Paolo
PY - 1992/9/21
Y1 - 1992/9/21
N2 - The biomolecular mechanisms that mediate signal transduction by type 11 (γ) interferon (IFN) are poorly understood. IFN-γ is a potent growth inhibitory cytokine also endowed with antiviral, immunomodulatory, and differentiating activities on various cell targets, including neural cells. IFN-γ induced a rapid and transient activation of phospholipase A2 in LAN-5, a human neuroblastoma cell line. A consequence of phospholipase A2 activation was the release of arachidonic acid and the generation of lysophospholipids from membrane phospholipids. Treatment of pre-labeled LAN-5 cells with a receptor-saturating concentration of IFN-γ led to a time-dependent release of [3H]arachidonic acid into the culture media and generation or [32P]lysophosphatidylcholine. Pretreatment of cultures with the phospholipase A2 inhibitor, bromophenacyl bromide, markedly inhibited both [3H]arachidonic acid release and lysophosphatidylcholine production induced by IFN-γ treatment. Pretreatment of LAN-5 cells with nordihydroguaiaretic acid, a lipoxygenase inhibitor, or with indomethacin, a cyclooxygenase inhibitor, amplified the release of[3H]arachidonic acid and production of lysophosphatidylcholine induced by non-saturating concentrations of IFN-γ. In parallel, and with the same time-dependent effect, a significant decrease in phosphatidylcholine labeling was observed in IFN-γ-treated cells, further indicating that a potential signal transduction mechanism of IFN-γ is the hydrolysis of membrane phosphatidylcholine by phospholipase A2.
AB - The biomolecular mechanisms that mediate signal transduction by type 11 (γ) interferon (IFN) are poorly understood. IFN-γ is a potent growth inhibitory cytokine also endowed with antiviral, immunomodulatory, and differentiating activities on various cell targets, including neural cells. IFN-γ induced a rapid and transient activation of phospholipase A2 in LAN-5, a human neuroblastoma cell line. A consequence of phospholipase A2 activation was the release of arachidonic acid and the generation of lysophospholipids from membrane phospholipids. Treatment of pre-labeled LAN-5 cells with a receptor-saturating concentration of IFN-γ led to a time-dependent release of [3H]arachidonic acid into the culture media and generation or [32P]lysophosphatidylcholine. Pretreatment of cultures with the phospholipase A2 inhibitor, bromophenacyl bromide, markedly inhibited both [3H]arachidonic acid release and lysophosphatidylcholine production induced by IFN-γ treatment. Pretreatment of LAN-5 cells with nordihydroguaiaretic acid, a lipoxygenase inhibitor, or with indomethacin, a cyclooxygenase inhibitor, amplified the release of[3H]arachidonic acid and production of lysophosphatidylcholine induced by non-saturating concentrations of IFN-γ. In parallel, and with the same time-dependent effect, a significant decrease in phosphatidylcholine labeling was observed in IFN-γ-treated cells, further indicating that a potential signal transduction mechanism of IFN-γ is the hydrolysis of membrane phosphatidylcholine by phospholipase A2.
KW - Indomethacin
KW - Interferon-γ
KW - Neuroblastoma
KW - Nordihydroguaiaretic acid (NDGA)
KW - Phospholipase A
UR - http://www.scopus.com/inward/record.url?scp=0026767325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026767325&partnerID=8YFLogxK
U2 - 10.1016/0014-5793(92)81136-A
DO - 10.1016/0014-5793(92)81136-A
M3 - Article
C2 - 1526278
AN - SCOPUS:0026767325
VL - 310
SP - 17
EP - 21
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -