Effect of PMA on Autophagy in Human Monocyte Cell-Line, THP-1

Abstract

THP-1 cells are human monocyte like cell line that is blocked at certain steps of the differentiation process and its differentiation into macrophages can be induced by addition of PMA. PMA activates Protein Kinase C (PKC) that mimics the physiological activator diacylglycerol (DAG) thus differentiation into macrophage occurs. These cells mimic the alveolar macrophages. So, is a good model to study tuberculosis. According to W.H.O. around 1.3 million people die of this disease every year. Mycobacterium tuberculosis the causative organism of this disease enters into the body through the airway passages. The alveolar macrophages phagocyte the bacteria. Once inside they escape degradation by preventing the phagosomes-lysosome fusion. Thus, they survive inside the phagosomes by inhibiting autophagy. To curtail this bacterial load, various host defence mechanisms like apoptosis, reactive oxygen and nitrogen species, phagosome-lysosome fusion and autophagy play a very important role. Autophagy in the cells is induced by ATP, vitamin D, cytokines. ATP is known to increase the intracellular calcium level that facilitates autophagy. Calcimining, an important calcium ionosphere increases the intracellular calcium level thus facilitates autophagy. Since autophagy plays an important role in curtailing bacterial load so we attempted to study the role of PMA in inducing autophagy in THP-1 cells.