New induction of leukotriene A4 hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes

Interleukin (IL)-4, IL-10, and IL-13, Th2 cell-derived cytokines, play majo r roles in the pathophysiology of allergic diseases. These cytokines up-reg ulate or down-regulate the production of arachidonic acid metabolites. In t his 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 LTB4 was measured by spe cific radioimmunoassay and high performance liquid chromatography. Messenge r RNA (mRNA) expression of cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxy genase (5-LO), and LTA(4) hydrolase, which were involved in the synthesis o f LTB4, was determined by reverse transcription-polymerase chain reaction a nd Northern blot analysis. Protein synthesis of their enzymes was determine d by Western blot analysis. IL-4 and IL-13 enhanced A23187-stimulated LTB4 synthesis and increased mRNA expression end protein synthesis of LTA(4) hyd rolase, 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 synth esis of LTB4, a potent chemotactic factor to PMNs, at the enzyme level of L TA(4) hydrolase, and this up-regulation mechanism may participate In the de velopment of allergic inflammation. (C) 2000 by The American Society of Hem atology.