Iaccio Annalisa, Cattaneo Fabio, Mauro Martina, Ammendola Rosario
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Arch Biochem Biophys. 2009 Jan 1;481(1):94-100. doi: 10.1016/j.abb.2008.10.026. Epub 2008 Oct 26.
Molecular mechanisms underlying the generation of reactive oxygen species in LL-37-stimulated cells are poorly understood. Previously, we demonstrated that in human fibroblasts the exposure to WKYMVm induced p47(phox) phosphorylation and translocation and, in turn, NADPH oxidase activation. These effects were mediated by the activation of the Formyl-peptide receptor-like 1 (FPRL1) and the downstream signaling involved ERKs phosphorylation and PKCalpha- and PKCdelta-activation. Since LL-37 uses FPRL1 as a receptor to mediate its action on several cell types, we investigated in LL-37-stimulated IMR90 cells molecular mechanisms involved in NADPH-dependent superoxide generation. The exposure to LL-37, which is expressed in fibroblasts, induced ERKs activation, p47(phox) phosphorylation and translocation as well as NADPH oxidase activation. These effects were prevented by pertussis toxin, PD098059 and WRWWWW, a FPRL1-selective antagonist. Furthermore, the stimulation with LL-37 of HEK293 cells, transfected to stably express FPRL1, induced a rapid activation of ERKs and p47(phox) phosphorylation.
LL-37刺激的细胞中产生活性氧的分子机制目前仍知之甚少。此前，我们证明，在人成纤维细胞中，暴露于WKYMVm会诱导p47(phox)磷酸化和易位，进而激活NADPH氧化酶。这些效应是由甲酰肽受体样1（FPRL1）的激活介导的，下游信号传导涉及ERK磷酸化以及PKCα和PKCδ的激活。由于LL-37利用FPRL1作为受体来介导其对多种细胞类型的作用，我们研究了LL-37刺激的IMR90细胞中与NADPH依赖性超氧化物生成相关的分子机制。暴露于成纤维细胞中表达的LL-37会诱导ERK激活、p47(phox)磷酸化和易位以及NADPH氧化酶激活。百日咳毒素、PD098059和FPRL1选择性拮抗剂WRWWWW可阻止这些效应。此外，用LL-37刺激稳定表达FPRL1的HEK293细胞会诱导ERK的快速激活和p47(phox)磷酸化。
