PAF induces gene expression of 5-lipoxygenase-activating protein (FLAP) in rat intestine

The biosynthesis of leukotrienes (LTs), lipid inflammatory mediators, depends on activation of 3-lipoxygenase (5-LO). FLAP has an essential role in the regulation of 5-LO to produce LTs. Our previous study has shown that LTs, especially LTC₄, may be secondary mediators involved in PAF-induced bowel injury. Here we examined the expression of the FLAP gene in the small intestine of anesthetized young S.D. rats after systemic administration of PAF (2-2.5 μg/kg, iv) or LPS (10 mg/kg, iv). The intestinal mRNA was extracted at various time points and tissue FLAP mRNA was quantified by northern blot analysis using a cDNA probe. We found that sham operated rats have a low level of constitutive expression of FLAP gene, which increased slowly (2 hr) with time. PAF rapidly induced FLAP gene expression within 30 min (1.6 fold of control), which reached 1.8 fold of control value at 60 min. (Most rats developed intestinal injury at 60 min). The effect of LPS is much slower than PAF. LPS minimally induced FLAP gene expression at 1 hr; the effect became apparent (1.3 fold of control) at 2 hr. Pretreatment of the rat with WEB2086 (1 mg/kg), a PAF antagonist, did not significantly prevent LPS-induced FLAP gene expression. Thus, PAF and LPS induce FLAP gene expression in the intestine, probably via independent pathways.