The antimicrobial peptide LL-37 enhances IL-8 release by human airway smooth muscle cells - 20/08/11
, Dennis K. Ninaber, BSc, Pieter S. Hiemstra, PhD, Klaus F. Rabe, MD, PhD
Reprint requests: Suzanne Zuyderduyn, MSc, Department of Pulmonology, Leiden University Medical Center, C3-P, PO Box 9600, 2300 RC Leiden, The Netherlands.Leiden, The Netherlands
Abstract |
Background |
Human airway smooth muscle (HASM) cells release various chemokines that are involved in recruitment of inflammatory cells, which can be found within or in the vicinity of the airway smooth muscle layer in patients with inflammatory lung diseases. Inflammatory cells contain antimicrobial peptides including the cathelicidin LL-37 and neutrophil defensins (HNP1-3).
Objective |
The aim of the study was to determine the effects of antimicrobial peptides on IL-8 (CXC chemokine ligand 8) release by HASM cells, and to study the underlying mechanisms.
Methods |
Human airway smooth muscle cells were stimulated with LL-37 and HNP1-3, and IL-8 protein and mRNA levels were determined by sandwich ELISA and PCR. Phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was detected by using Western blot.
Results |
LL-37 enhanced IL-8 release by HASM cells, which was dependent on ERK1/2 activation. Receptors known to be involved in LL-37–induced signaling, including the epidermal growth factor receptor and formyl peptide receptors, were not involved in LL-37 signaling in HASM cells. The purinergic receptor antagonist suramin did block LL-37–induced ERK1/2 phosphorylation and IL-8 release, and expression of mRNA for the purinergic receptor P2X7 was detected in HASM cells. HNP1-3 did increase ERK1/2 phosphorylation, but did not enhance IL-8 release by HASM cells.
Conclusion |
These data show that HASM cells respond to the antimicrobial peptide LL-37 by releasing IL-8, suggesting that LL-37 is a regulator of the inflammatory process in various inflammatory lung diseases by enhancing IL-8 production.
Clinical implications |
LL-37 released by inflammatory cells may amplify inflammation through induction of IL-8 release by airway smooth muscle.
Le texte complet de cet article est disponible en PDF.Key words : Human airway smooth muscle cells, asthma, chronic obstructive pulmonary disease, inflammation, antimicrobial peptides, chemokines, IL-8, extracellular signal-regulated kinase
Abbreviations used : COPD, EGFR, ERK, FPRL-1, HASM, hCAP18, HNP, MAPK, tBoc-MLP
Plan
| Supported by an unrestricted educational grant from AstraZeneca, Lund, Sweden. Disclosure of potential conflict of interest: P. S. Hiemstra has received grant support from AltanaPharma, Novartis, Bayer, AstraZeneca, Pfizer, MSD, Exhale Therapeutics, and GlaxoSmithKline. K. F. Rabe has consultant arrangements, participated on the advisory board, and received lecture fees from AstraZeneca, Boehringer, Chiesi Pharmaceuticals, Pfizer, Novartis, AltanaPharma, MSD, and GlaxoSmithKline, and has received grant support from AltanaPharma, Novartis, Bayer, AstraZeneca, Pfizer, MSD, Exhale Therapeutics, and GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest. |
Vol 117 - N° 6
P. 1328-1335 - juin 2006 Retour au numéro
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