title: New induction of leukotriene A(4) hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes.
abstract: Interleukin (IL)-4, IL-10, and IL-13, Th2 cell-derived cytokines, play major roles in the pathophysiology of allergic diseases. These cytokines up-regulate or down-regulate the production of arachidonic acid metabolites. In this study, we have investigated the effect of IL-4, IL-10, IL-13, and other cytokines on A23187-stimulated synthesis of leukotriene (LT) B(4) in human polymorphonuclear leukocytes (PMNs). Production of LTB(4) was measured by specific radioimmunoassay and high performance liquid chromatography. Messenger RNA (mRNA) expression of cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LO), and LTA(4) hydrolase, which were involved in the synthesis of LTB(4), was determined by reverse transcription-polymerase chain reaction and Northern blot analysis. Protein synthesis of their enzymes was determined by Western blot analysis. IL-4 and IL-13 enhanced A23187-stimulated LTB(4) synthesis and increased mRNA expression and protein synthesis of LTA(4) hydrolase, but not those of cPLA(2) or 5-LO. These results indicate that IL-4 and IL-13 transcriptionally or post-transcriptionally up-regulate the synthesis of LTB(4), a potent chemotactic factor to PMNs, at the enzyme level of LTA(4) hydrolase, and this up-regulation mechanism may participate in the development of allergic inflammation. (Blood. 2000;96:601-609)
authors.affiliation: Departments of Pediatrics and Microbiology, Saga Medical School, Saga, Japan. g9609@post.saga-med.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Zaitsu
authors.forename: Y
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
authors.forename: A
authors.initials: A
authors.lastname: Kukita
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: R
authors.initials: R
authors.lastname: Hayasaki
authors.forename: E
authors.initials: E
authors.lastname: Muro
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Ichimaru
authors.forename: O
authors.initials: O
authors.lastname: Kohashi
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis; D009504:Neutrophils / Q000201:enzymology*; D010741:Phospholipases A / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018793:Interleukin-13; D007476:Ionophores; D012333:RNA, Messenger; D016753:Interleukin-10; D007975:Leukotriene B4; D015847:Interleukin-4; D000001:Calcimycin; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase