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http://dx.doi.org/10.5352/JLS.2017.27.2.217

Carbon Monoxide Inhibits PMA-induced Differentiation in Human Monocytic THP-1 Cells  

Kim, Da Sol (Department of Microbiology & Immunology, Pusan National University College of Medicine)
Lee, Mi Sun (Department of Microbiology & Immunology, Pusan National University College of Medicine)
Kim, Han Sol (Department of Premedicine, Pusan National University College of Medicine)
Lee, Hye Yun (Department of Premedicine, Pusan National University College of Medicine)
Kim, Oh Yun (Department of Premedicine, Pusan National University College of Medicine)
Kang, Ye Rin (Department of Premedicine, Pusan National University College of Medicine)
Sohn, Dong Hyun (Department of Microbiology & Immunology, Pusan National University College of Medicine)
Kim, Koanhoi (Department of Pharmacology, Pusan National University College of Medicine)
Park, Young Chul (Department of Microbiology & Immunology, Pusan National University College of Medicine)
Publication Information
Journal of Life Science / v.27, no.2, 2017 , pp. 217-224 More about this Journal
Abstract
Carbon monoxide (CO), a reaction product of cytoprotective enzyme heme oxygenase-1 (HO-1), is a gaseous messenger with anti-proliferative, anti-apoptotic, and anti-inflammatory actions in many cell types. Here, we investigated the role of CO on the process of monocyte differentiation induced by phorbol 12-myristate 13-acetate (PMA) in human monocytic THP-1 cells. CORM-2 (tricarbonyldichlororuthenium (II) dimer, $Ru2Cl_4(CO)_6$), a CO-releasing compound, decreased a marked cell adherence with a slight reduction of proliferation in monocytic THP-1 cells treated with PMA. And, CORM-2 significantly inhibited expression of differentiation markers such as CD14, CD11b plus CD18 (macrophage-1 antigen, Mac-1 or complement receptor 3, CR3) and phagocytosis of carboxylate-modified red fluorescent latex beads, in PMA-stimulated THP-1 cells. For the further experiments, differentiation of PMA-treated cells was enhanced after the initial 2 days stimulus by removing the PMA-containing media then incubating the cells in fresh media for a another 4 days. And, we observed the secretion of inflammatory cytokines and phagocytosis in differentiated macrophages. Treatment with CORM-2 significantly abolished the secretion of IL-6, $TNF-{\alpha}$ and phagocytosis using fluorescence-conjugated E. coli (K-12 strain) bioparticles in lipopolysaccharide (LPS)-stimulated differentiated macrophages. In conclusion, these results suggest that CO inhibits the differentiation of monocytic THP-1 cells as well as the activation of differentiated macrophages.
Keywords
CO; differentiation; phagocytosis; PMA; THP-1 cells;
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