Nakano Yoshiteru
   Department   School of Medicine  Neurosurgery, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title 5-Aminolevulinic acid suppresses prostaglandin E2 production by murine macrophages and enhances macrophage cytotoxicity against glioma.
Journal Formal name:World neurosurgery
Abbreviation:World Neurosurg
ISSN code:18788769/18788750
Volume, Issue, Page 127,669-676頁
Author and coauthor Nakano Yoshiteru, Kitagawa Takehiro, Osada Yoshio, Tanaka Tohru, Nishizawa Shigeru, Yamamoto Junkoh
Publication date 2019/07
Summary BACKGROUND:5-aminolevulinic acid (ALA) induces accumulation of high 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 (LPS), and 20% glioma-conditioned medium. Levels of immunosuppressive prostaglandin (PG) E2, 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, 0.5 mM) and LPS (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 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-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 down-regulation of COX-2 and mPGES-1 expression levels. This is a novel mechanism to induce effective immune response against glioma in macrophages.
DOI 10.1016/j.wneu.2019.03.240
PMID 30947012