PT  - JOURNAL ARTICLE
AU  - Stefen Boehme
AU  - John Ludka
AU  - Danielle DiTirro
AU  - Ana Lucia Coelho
AU  - Cory Hogaboam
AU  - Tai Wei Ly
AU  - Kevin Bacon
TI  - RC kinase: A novel kinase expressed by alveolar macrophages that may play a role in COPD and IPF
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P2124
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P2124.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P2124.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - We have characterized a novel serine/threonine protein kinase, called RC kinase, whose expression is upregulated in COPD patients. Examination of RC kinase mRNA tissue distribution showed a limited expression pattern restricted mainly to the lungs and trachea. Immunohistochemical analysis with a monoclonal antibody revealed expression in CD68+ alveolar macrophage and bronchial epithelial cells. Various cell lines upregulated RC kinase expression upon exposure to cigarette smoke extract, or conditions of oxidative or endoplasmic reticulum stress, and this correlated with the production of IL-8. In acute (4 day) and sub-chronic (14 day) cigarette smoke-induced murine models of COPD, treatment with either intra-tracheally delivered RC kinase siRNA or orally administered novel and specific small molecule inhibitors caused a significant reduction in BAL neutrophilia, as well as decreased levels of KC and CCL-20. There was also a marked reduction in the amount of pulmonary inflammation. In a murine adoptive transfer model of idiopathic pulmonary fibrosis, both siRNA and small molecule antagonist treatment significantly inhibited hydroxyproline production, inflammation and cellular and biochemical markers of fibrosis. Taken together, these results strongly suggest that inhibition of RC kinase may provide a novel therapeutic approach for the treatment of COPD and IPF.