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Novel signaling function of hCLCA1 in airway macrophages activation (1095.2)
Author(s) -
Ching John,
Loewen Matthew
Publication year - 2014
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.28.1_supplement.1095.2
Subject(s) - microbiology and biotechnology , inflammation , macrophage , hek 293 cells , function (biology) , monocyte , cytokine , chemistry , signal transduction , cell culture , immunology , biology , biochemistry , in vitro , genetics
The CLCA gene family produces both secreted and membrane‐associated proteins that modulate ion‐channel function, drive mucus production and have a poorly understood pleiotropic effect on airway inflammation. In airway inflammation, the primary up‐regulated human CLCA ortholog is hCLCA1. Here we show that secreted hCLCA1 is able to activate macrophages, inducing them to express cytokines and to undertake a pivotal role in airway inflammation. Conditioned media collected from HEK293 cells heterologously expressing hCLCA1 increased the expression of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IL‐8) in U‐937 monocyte‐macrophage cell line. Similar pro‐inflammatory response was achieved in primary porcine alveolar macrophages activated with hCLCA1 conditioned media, showing that the effect was not cell line dependent. Immuno‐purified hCLCA1 at physiologically relevant concentration of ~100 pg/mL was also able to elicit pro‐inflammatory response in macrophages. These findings demonstrating that secreted hCLCA1 is able to function as a signaling molecule and to regulate cytokine expression in macrophages. Grant Funding Source : NSERC