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Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia.
J Neuroimmunol. 2006 Mar; 172(1-2):112-20.JN

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 PGE2 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 PGE2 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 PGE2 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 PGE2 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.

Authors+Show Affiliations

Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka 812-8582, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16371234

Citation

Zhang, Jian, et al. "Involvement of COX-1 and Up-regulated Prostaglandin E Synthases in Phosphatidylserine Liposome-induced Prostaglandin E2 Production By Microglia." Journal of Neuroimmunology, vol. 172, no. 1-2, 2006, pp. 112-20.
Zhang J, Fujii S, Wu Z, et al. Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. J Neuroimmunol. 2006;172(1-2):112-20.
Zhang, J., Fujii, S., Wu, Z., Hashioka, S., Tanaka, Y., Shiratsuchi, A., Nakanishi, Y., & Nakanishi, H. (2006). Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. Journal of Neuroimmunology, 172(1-2), 112-20.
Zhang J, et al. Involvement of COX-1 and Up-regulated Prostaglandin E Synthases in Phosphatidylserine Liposome-induced Prostaglandin E2 Production By Microglia. J Neuroimmunol. 2006;172(1-2):112-20. PubMed PMID: 16371234.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2005/12/20/ PY - 2005/07/01/received PY - 2005/11/09/accepted PY - 2005/12/24/pubmed PY - 2006/5/10/medline PY - 2005/12/24/entrez SP - 112 EP - 20 JF - Journal of neuroimmunology JO - J. Neuroimmunol. VL - 172 IS - 1-2 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 PGE2 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 PGE2 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 PGE2 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 PGE2 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. SN - 0165-5728 UR - https://www.unboundmedicine.com/medline/citation/16371234/Involvement_of_COX_1_and_up_regulated_prostaglandin_E_synthases_in_phosphatidylserine_liposome_induced_prostaglandin_E2_production_by_microglia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-5728(05)00487-X DB - PRIME DP - Unbound Medicine ER -