Inverse regulation of lipid-peroxidizing and hydroperoxyl lipid-reducing enzymes by interleukins 4 and 13

12/15-lipoxygenases and phospholipid hydroperoxide glutathione peroxidases are opposite enzymes balancing the intracellular concentration of hydropero xy lipids. We studied the regulation of both enzymes by interleukins 4 and 13 and found an inverse response. When human lung carcinoma cells A549 were cultured in vitro in the presence of these cytokines, an up-regulation of the 12/15-lipoxygenase and a down-regulation of the phospholipid hydroperox ide glutathione peroxidase were observed, A similar inverse regulation was found in! human peripheral monocytes, Interleukin 4-treated A549 cells exhi bited an impaired capability of reducing exogenous hydroperoxyl lipids and their levels of endogenous lipid hydroperoxides were markedly increased. To find out whether these regulatory processes also occur in vivo, arachidoni c acid oxygenase and phospholipid hydroperoxide glutathione peroxidase acti vity was assayed in various tissues of transgenic mice that systemically ov erexpress interleukin 4, In lung, spleen, kidney, and heart, an increased a rachidonic acid oxygenase activity was detected when transgenic mice were c ompared with inbred controls, The phospholipid hydroperoxide glutathione pe roxidase activity was impaired in lung, liver, and spleen of the transgenic animals. These data indicate that lipid-peroxidizing and lipid peroxide-re ducing enzymes are inversely regulated in various mammalian cells, Up-regul ation of the 12./15-lipoxygenase and simultaneous down-regulation of the ph ospholipid hydroperoxide glutathione peroxidase may lead to an increased ox idizing potential, which is reflected by an augmented intracellular peroxid e tone.