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5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production by Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma.
World Neurosurg. 2019 Jul; 127:e669-e676.WN

Abstract

BACKGROUND

5-Aminolevulinic acid (5-ALA) induces the accumulation of a large amount of protoporphyrin IX (PpIX) in tumors, which has been used in the treatment of several cancers. 5-ALA is commonly used for fluorescence-guided tumor resection in clinical neurosurgery and for photodynamic therapy based on the generation of cytotoxic oxygen.

OBJECTIVE

The purpose of this study was to identify the mechanisms of 5-ALA-induced immune response in macrophages in malignant glioma.

METHODS

Intracellular levels of 5-ALA-induced PpIX in C3H/HeN murine peritoneal macrophages were measured by the median fluorescence intensity using flow cytometry and confocal laser scanning microscopy. Macrophages were cultured in vitro with or without 0.5 mM 5-ALA, 0.1 μg/mL lipopolysaccharide, and 20% glioma-conditioned medium. Levels of immunosuppressive prostaglandin E2 (PGE2), interleukin-10, and transforming growth factor β were measured using enzyme immunoassay in the culture supernatant. In addition, macrophages and RSV-M mouse glioma cells were co-cultured in vitro with cell culture inserts with or without 5-ALA (0.1 and 0.5 mM) and lipopolysaccharide (0.1 μg/mL).

RESULTS

We found that 5-ALA-induced PpIX accumulated in macrophages and significantly suppressed PGE2 production and expression of both cyclooxygenase-2 and microsomal prostaglandin E synthase-1. 5-ALA treatment also suppressed PGE2 production by glioma-conditioned medium. 5-ALA suppressed RSV-M glioma cell proliferation in a concentration-dependent manner.

CONCLUSIONS

These results indicate that 5-ALA suppressed PGE2 production by macrophages via the downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression levels. This is a novel mechanism to induce effective immune response against glioma in macrophages.

Authors+Show Affiliations

Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: yo-naka@med.uoeh-u.ac.jp.Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.SBI Pharmaceuticals Co., Ltd., Minato-Ku, Tokyo, Japan.Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30947012

Citation

Nakano, Yoshiteru, et al. "5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production By Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma." World Neurosurgery, vol. 127, 2019, pp. e669-e676.
Nakano Y, Kitagawa T, Osada Y, et al. 5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production by Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma. World Neurosurg. 2019;127:e669-e676.
Nakano, Y., Kitagawa, T., Osada, Y., Tanaka, T., Nishizawa, S., & Yamamoto, J. (2019). 5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production by Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma. World Neurosurgery, 127, e669-e676. https://doi.org/10.1016/j.wneu.2019.03.240
Nakano Y, et al. 5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production By Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma. World Neurosurg. 2019;127:e669-e676. PubMed PMID: 30947012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production by Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma. AU - Nakano,Yoshiteru, AU - Kitagawa,Takehiro, AU - Osada,Yoshio, AU - Tanaka,Tohru, AU - Nishizawa,Shigeru, AU - Yamamoto,Junkoh, Y1 - 2019/04/01/ PY - 2019/02/02/received PY - 2019/03/22/revised PY - 2019/03/23/accepted PY - 2019/4/5/pubmed PY - 2020/1/15/medline PY - 2019/4/5/entrez KW - 5-Aminolevulinic acid KW - COX-2 KW - Glioma KW - Prostaglandin E(2) KW - mPGES-1 SP - e669 EP - e676 JF - World neurosurgery JO - World Neurosurg VL - 127 N2 - BACKGROUND: 5-Aminolevulinic acid (5-ALA) induces the accumulation of a large amount of protoporphyrin IX (PpIX) in tumors, which has been used in the treatment of several cancers. 5-ALA is commonly used for fluorescence-guided tumor resection in clinical neurosurgery and for photodynamic therapy based on the generation of cytotoxic oxygen. OBJECTIVE: The purpose of this study was to identify the mechanisms of 5-ALA-induced immune response in macrophages in malignant glioma. METHODS: Intracellular levels of 5-ALA-induced PpIX in C3H/HeN murine peritoneal macrophages were measured by the median fluorescence intensity using flow cytometry and confocal laser scanning microscopy. Macrophages were cultured in vitro with or without 0.5 mM 5-ALA, 0.1 μg/mL lipopolysaccharide, and 20% glioma-conditioned medium. Levels of immunosuppressive prostaglandin E2 (PGE2), interleukin-10, and transforming growth factor β were measured using enzyme immunoassay in the culture supernatant. In addition, macrophages and RSV-M mouse glioma cells were co-cultured in vitro with cell culture inserts with or without 5-ALA (0.1 and 0.5 mM) and lipopolysaccharide (0.1 μg/mL). RESULTS: We found that 5-ALA-induced PpIX accumulated in macrophages and significantly suppressed PGE2 production and expression of both cyclooxygenase-2 and microsomal prostaglandin E synthase-1. 5-ALA treatment also suppressed PGE2 production by glioma-conditioned medium. 5-ALA suppressed RSV-M glioma cell proliferation in a concentration-dependent manner. CONCLUSIONS: These results indicate that 5-ALA suppressed PGE2 production by macrophages via the downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression levels. This is a novel mechanism to induce effective immune response against glioma in macrophages. SN - 1878-8769 UR - https://www.unboundmedicine.com/medline/citation/30947012/5_Aminolevulinic_Acid_Suppresses_Prostaglandin_E2_Production_by_Murine_Macrophages_and_Enhances_Macrophage_Cytotoxicity_Against_Glioma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1878-8750(19)30920-9 DB - PRIME DP - Unbound Medicine ER -