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hCLCA1 Modulates Macrophage Activation
Author(s) -
Ching John C.H.,
Loewen Matthew E.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1215.5
Subject(s) - microbiology and biotechnology , inflammation , macrophage , immune system , alveolar macrophage , signal transduction , cytokine , biology , immunology , receptor , chemistry , in vitro , biochemistry
Induced by airway inflammation, the CLCA gene family products exist both as secreted and membrane‐associated proteins. The proteins modulate ion channel function, drive mucus production and generally have a pleotropic effect on airway inflammation. How CLCAs deliver such a pleotropic effect on airway inflammation is poorly understood. Here we show that hCLCA1, the primary up‐regulated human CLCA orthologue in airway inflammation, is able to modulate macrophage activation. In order for a macrophage to undertake a role of either host defense, wound healing or immune regulation, it must become “activated”. This is usually a receptor driven signal transduction event resulting in gene transcription of cytokines. Using primary porcine alveolar macrophages and the U‐937 macrophage cell model, we were able to show that conditioned media with hCLCA1 significantly increased macrophage activation over control. The pro‐inflammatory cytokines IL‐1beta, IL‐6, TNF‐alpha, IL‐8 were increased, and the anti‐inflammatory cytokine IL‐10 was decreased in the U‐937 cell line. We found this effect to be independent of hCLCA1's metalloprotease domain. Subsequent purification of hCLCA1 produced a similar response demonstrating that the effect is primarily due to hCLCA1. These are the first findings demonstrating that hCLCA1 can deliver an immune modulating effect as a signaling molecule. Funding: SHRF, EHRF and NSERC