Abstract
After engulfment of apoptotic cells through phosphatidylserine (PS)-mediated recognition, microglia secrete prostaglandin E2 (PGE2), a potent anti-inflammatory molecule in the central nervous system. Despite the clinical significance, the mechanism underlying PGE 2 production by phagocytosis of apoptotic cells is poorly understood. In the present study, we used PS liposomes to elucidate the phagocytic pathway for PGE2 production in microglia, because PS liposomes mimic the effects of apoptotic cells on microglia/macrophages. The level of PGE 2 in the culture medium of primary cultured rat microglia was significantly increased by PS liposomes treatment but not by phosphatidylcholine liposomes treatment. The specific ligand for class B scavenger receptor (SR-B), high density lipoprotein, significantly suppressed PS liposome-induced PGE 2 production. PS liposomes were immediately phagocytosed by microglia and sorted to endosomes/lysosomes. Cyclooxygenase (COX)-2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced by treatment with lipopolysaccharide (LPS) but not with PS liposomes. On the other hand, mPGES-2 and cytosolic PGES (cPGES) that are functionally coupled with COX-1 were upregulated after treatment with PS liposomes or LPS. Furthermore, PS liposome-induced PGE2 production was significantly suppressed by indomethacin, a preferential COX-1 inhibitor, but not by NS-398, a selective COX-2 inhibitor. PS liposomes induced activation of p44/p42 extracellular signal-regulated kinase (ERK) but not p38 mitogen-activated protein kinase in SR-BI independent manner. These observations strongly suggest that the up-regulation of terminal PGESs that are preferentially coupled with COX-1, especially mPGES-2, plays the pivotal role in PS liposome-induced PGE 2 production by microglia. Although SR-BI plays an essential role in PS liposome-induced PGE2 production, other PS-recognizing receptors, possibly PS-specific receptor, could also promote PGE2 production by transducing intracellular signals including p44/p42 ERK after PS liposomes treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 112-120 |
| Number of pages | 9 |
| Journal | Journal of Neuroimmunology |
| Volume | 172 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Mar 1 2006 |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Neurology
- Clinical Neurology
Cite this
Involvement of COX-1 and up-regulated prostaglandin e synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. / Zhang, Jian; Fujii, Shunsuke; Wu, Zhou; Hashioka, Sadayuki; Tanaka, Yoshitaka; Shiratsuchi, Akiko; Nakanishi, Yoshinobu; Nakanishi, Hiroshi.
In: Journal of Neuroimmunology, Vol. 172, No. 1-2, 01.03.2006, p. 112-120.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of COX-1 and up-regulated prostaglandin e synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia
AU - Zhang, Jian
AU - Fujii, Shunsuke
AU - Wu, Zhou
AU - Hashioka, Sadayuki
AU - Tanaka, Yoshitaka
AU - Shiratsuchi, Akiko
AU - Nakanishi, Yoshinobu
AU - Nakanishi, Hiroshi
PY - 2006/3/1
Y1 - 2006/3/1
N2 - After engulfment of apoptotic cells through phosphatidylserine (PS)-mediated recognition, microglia secrete prostaglandin E2 (PGE2), a potent anti-inflammatory molecule in the central nervous system. Despite the clinical significance, the mechanism underlying PGE 2 production by phagocytosis of apoptotic cells is poorly understood. In the present study, we used PS liposomes to elucidate the phagocytic pathway for PGE2 production in microglia, because PS liposomes mimic the effects of apoptotic cells on microglia/macrophages. The level of PGE 2 in the culture medium of primary cultured rat microglia was significantly increased by PS liposomes treatment but not by phosphatidylcholine liposomes treatment. The specific ligand for class B scavenger receptor (SR-B), high density lipoprotein, significantly suppressed PS liposome-induced PGE 2 production. PS liposomes were immediately phagocytosed by microglia and sorted to endosomes/lysosomes. Cyclooxygenase (COX)-2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced by treatment with lipopolysaccharide (LPS) but not with PS liposomes. On the other hand, mPGES-2 and cytosolic PGES (cPGES) that are functionally coupled with COX-1 were upregulated after treatment with PS liposomes or LPS. Furthermore, PS liposome-induced PGE2 production was significantly suppressed by indomethacin, a preferential COX-1 inhibitor, but not by NS-398, a selective COX-2 inhibitor. PS liposomes induced activation of p44/p42 extracellular signal-regulated kinase (ERK) but not p38 mitogen-activated protein kinase in SR-BI independent manner. These observations strongly suggest that the up-regulation of terminal PGESs that are preferentially coupled with COX-1, especially mPGES-2, plays the pivotal role in PS liposome-induced PGE 2 production by microglia. Although SR-BI plays an essential role in PS liposome-induced PGE2 production, other PS-recognizing receptors, possibly PS-specific receptor, could also promote PGE2 production by transducing intracellular signals including p44/p42 ERK after PS liposomes treatment.
AB - After engulfment of apoptotic cells through phosphatidylserine (PS)-mediated recognition, microglia secrete prostaglandin E2 (PGE2), a potent anti-inflammatory molecule in the central nervous system. Despite the clinical significance, the mechanism underlying PGE 2 production by phagocytosis of apoptotic cells is poorly understood. In the present study, we used PS liposomes to elucidate the phagocytic pathway for PGE2 production in microglia, because PS liposomes mimic the effects of apoptotic cells on microglia/macrophages. The level of PGE 2 in the culture medium of primary cultured rat microglia was significantly increased by PS liposomes treatment but not by phosphatidylcholine liposomes treatment. The specific ligand for class B scavenger receptor (SR-B), high density lipoprotein, significantly suppressed PS liposome-induced PGE 2 production. PS liposomes were immediately phagocytosed by microglia and sorted to endosomes/lysosomes. Cyclooxygenase (COX)-2 and membrane-bound prostaglandin E synthase-1 (mPGES-1) were induced by treatment with lipopolysaccharide (LPS) but not with PS liposomes. On the other hand, mPGES-2 and cytosolic PGES (cPGES) that are functionally coupled with COX-1 were upregulated after treatment with PS liposomes or LPS. Furthermore, PS liposome-induced PGE2 production was significantly suppressed by indomethacin, a preferential COX-1 inhibitor, but not by NS-398, a selective COX-2 inhibitor. PS liposomes induced activation of p44/p42 extracellular signal-regulated kinase (ERK) but not p38 mitogen-activated protein kinase in SR-BI independent manner. These observations strongly suggest that the up-regulation of terminal PGESs that are preferentially coupled with COX-1, especially mPGES-2, plays the pivotal role in PS liposome-induced PGE 2 production by microglia. Although SR-BI plays an essential role in PS liposome-induced PGE2 production, other PS-recognizing receptors, possibly PS-specific receptor, could also promote PGE2 production by transducing intracellular signals including p44/p42 ERK after PS liposomes treatment.
UR - http://www.scopus.com/inward/record.url?scp=33244479399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33244479399&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2005.11.008
DO - 10.1016/j.jneuroim.2005.11.008
M3 - Article
C2 - 16371234
AN - SCOPUS:33244479399
VL - 172
SP - 112
EP - 120
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
SN - 0165-5728
IS - 1-2
ER -