title: 5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction.
abstract: 5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy.
authors.affiliation: Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.affiliation: Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nishio
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.affiliation: SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: ri-k@ncchd.go.jp.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
mesh_terms: D000622:Aminolevulinic Acid / Q000378:metabolism / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006648:Histocompatibility / Q000187:drug effects*; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology; D011524:Protoporphyrins / Q000378:metabolism; D015398:Signal Transduction; D014184:Transplantation, Homologous
chemical_list: D007155:Immunologic Factors; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: 5-Aminolevulinic acid; HO-1; Nrf2