PT  - JOURNAL ARTICLE
AU  - Suzanne Zuyderduyn
AU  - DennisK. Ninaber
AU  - PieterS. Hiemstra
AU  - KlausF. Rabe
TI  - Role of purinergic receptors in the activation of human airway smooth muscle cells by the antimicrobial peptide LL-37
AID  - 10.1183/09059180.00010114
DP  - 2006 Dec 01
TA  - European Respiratory Review
PG  - 182--184
VI  - 15
IP  - 101
4099  - http://err.ersjournals.com/content/15/101/182.short
4100  - http://err.ersjournals.com/content/15/101/182.full
SO  - EUROPEAN RESPIRATORY REVIEW2006 Dec 01; 15
AB  - Inflammatory cells that infiltrate and surround the airway smooth muscle (ASM) layer express antimicrobial peptides including the cathelicidin LL-37. LL-37 has been shown to activate epithelial cells by transactivation of the epidermal growth factor receptor (EGFR). Previously, we have shown that LL-37-induced IL-8 release by ASM cells was not dependent on either formyl peptide receptors or the EGFR (ATS 2005). In monocytes LL-37 induces processing of IL-1β through activation of the purinergic P2X7 receptor. Therefore, the aim of our study was to evaluate the role of purinergic receptors in LL-37-induced activation of ASM cells, and to explore the involvement of several intracellular signalling pathways. ASM cells were cultured and serum-deprived 24 hours before stimulation with LL-37 (10 μg·ml−1). The purinergic receptor antagonist suramin and inhibitors of ERK1/2, p38, Src and PI3K were preincubated for one hour. ERK1/2 phosphorylation was assessed by Western Blot, and IL-8 release was determined in supernatants using a sandwich ELISA. RT-PCR was performed for P2X7 on untreated ASM cells. LL-37 induced ERK1/2 phosphorylation and IL-8 release; both were inhibited by suramin (IL-8: 86%). Inhibitors of ERK1/2, p38 and Src signalling also reduced LL-37-induced IL-8 release (by 67%, 63% and 76%, respectively), suggesting a role for these pathways. P2X7 mRNA was expressed in ASM cells. These data show that LL-37-induced IL-8 release is mediated via purinergic receptors, ERK1/2 activation, p38 and Src signalling. Our PCR data are in line with the hypothesis that also in ASM P2X7 is the purinergic receptor involved in LL-37 signalling, although this needs further investigation.