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Domain of hCLCA1 that is responsible for macrophage activation
Author(s) -
Ching John C.H.,
Loewen Matthew E
Publication year - 2016
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.30.1_supplement.969.15
Subject(s) - inflammation , microbiology and biotechnology , macrophage , immune system , immunology , biology , chemistry , in vitro , biochemistry
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. The mechanism of how hCLCA1 regulates airway inflammation remains unclear. However, hCLCA1 is highly expressed in airway diseases in which alveolar macrophages’ are central to disease progression. Thus, it is possible that hCLCA1's role in airway inflammation is to regulate the immune response of macrophages. Previously, we showed that secreted hCLCA1 is able to activate macrophages, inducing them to express cytokines and to undertake a pivotal role in airway inflammation. In this study, we have purified the functional domains of hCLCA1, and we activated macrophages with these domains. There are three functional domains in hCLCA1 (hydrolase domain, von Willebrand type A domain, and fibronectin type III domain), and we found that one of these hCLCA1's domains significantly induced the expression of pro‐inflammatory cytokines in macrophages. To further investigate this activation, we have also found the cell signaling pathways that are involved in this activation Support or Funding Information Natural Sciences and Engineering Research Council (NSERC) 371364/2010 to MEL