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)
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Authors | M Zaitsu, Y Hamasaki, M Matsuo, A Kukita, K Tsuji, M Miyazaki, R Hayasaki, E Muro, S Yamamoto, I Kobayashi, T Ichimaru, O Kohashi, S Miyazaki |
Journal | Blood
(Blood)
Vol. 96
Issue 2
Pg. 601-9
(Jul 15 2000)
ISSN: 0006-4971 [Print] United States |
PMID | 10887124
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Interleukin-13
- Ionophores
- RNA, Messenger
- Interleukin-10
- Leukotriene B4
- Interleukin-4
- Calcimycin
- Arachidonate 5-Lipoxygenase
- Phospholipases A
- Epoxide Hydrolases
- leukotriene A4 hydrolase
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Topics |
- Arachidonate 5-Lipoxygenase
(genetics)
- Blotting, Northern
- Blotting, Western
- Calcimycin
(pharmacology)
- Chromatography, High Pressure Liquid
- Enzyme Induction
- Epoxide Hydrolases
(biosynthesis, genetics)
- Humans
- Interleukin-10
(pharmacology)
- Interleukin-13
(pharmacology)
- Interleukin-4
(pharmacology)
- Ionophores
(pharmacology)
- Leukotriene B4
(biosynthesis)
- Neutrophils
(enzymology)
- Phospholipases A
(genetics)
- RNA, Messenger
(analysis)
- Reverse Transcriptase Polymerase Chain Reaction
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