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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 601-609
New induction of leukotriene
A4 hydrolase by interleukin-4 and interleukin-13 in human
polymorphonuclear leukocytes
Masafumi Zaitsu,
Yuhei Hamasaki,
Muneaki Matsuo,
Akiko Kukita,
Kosuke Tsuji,
Michiko Miyazaki,
Rika Hayasaki,
Eriko Muro,
Shuichi Yamamoto,
Ikuko Kobayashi,
Tomohiro Ichimaru,
Osamu Kohashi, and
Sumio Miyazaki
From the Departments of Pediatrics and Microbiology, Saga Medical
School, Saga, Japan.
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) B4 in human polymorphonuclear
leukocytes (PMNs). Production of LTB4 was measured by
specific radioimmunoassay and high performance liquid chromatography.
Messenger RNA (mRNA) expression of cytosolic phospholipase
A2 (cPLA2), 5-lipoxygenase (5-LO), and
LTA4 hydrolase, which were involved in the synthesis of
LTB4, 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 LTB4 synthesis
and increased mRNA expression and protein synthesis of LTA4
hydrolase, but not those of cPLA2 or 5-LO.
These results indicate that IL-4 and IL-13 transcriptionally or
post-transcriptionally up-regulate the synthesis of LTB4, a potent chemotactic factor to PMNs, at the enzyme level of
LTA4 hydrolase, and this up-regulation mechanism may
participate in the development of allergic inflammation.
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