Purified sardine and king crab trypsin display individual differences in PAR-2-, NF-kB-, and IL-8 signaling
Submitted manuscript version. Published version available in Toxicological & Environmental Chemistry, Volume 93, Issue 10, 2011 (PDF)
Respiratory symptoms occur in workers processing a great variety of seafood. Studies previously showed that salmon trypsin increases transcriptional activity of NF-κB and induces secretion of IL-8 from airway epithelial cells by activating PAR-2. The aim of this study was to explore if purified trypsins from king crab (Paralithodes camtschaticus) and sardine (Sardinops melanostictus) are able to induce similar effects in cell stimulation assays. The knowledge that crustaceans seem to display dissimilar irritant potency compared to fish inspired us to investigate if one could detect differences in intracellular signaling pathways coupled to IL-8 in human airway epithelial cells (A549). Both sardine and king crab trypsin induced secretion of IL-8 from human airway epithelial cells in a concentration-dependent manner and increased transcriptional activity of NF-κB. With the use of siRNA data indicate that these effects are both mediated, at least partly, through the activation of PAR-2. Additionally, the king crab and sardine trypsin display individual differences in transformation of the NF-κB signal into subsequent IL-8 secretion. The contribution of MEK/ERK, p38, and NF-κB to the secretion of IL-8 following stimulation with sardine and king crab trypsins were examined with the use of specific inhibitors. The results demonstrated that MEK/ERK and NF-κB are both required for sardine and king crab trypsin-induced secretion of IL-8 but via separate pathways. P38 was also found to contribute to the secretion of IL-8 seemingly by NF-κB-dependent processes.
This article is part of Anett Kristin Larsen's doctoral thesis. Available at http://hdl.handle.net/10037/2892
SiteringToxicological & Environmental Chemistry 93(2011) nr. 10 s. 1991-2011
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