Effect of Calcimycin Regulated Autophagy on Nuclear Receptor HNF-4a Expression in THP-1 Cells

Abstract

Nuclear receptors (NRs) include 49 members and belong to family that function as ligand-inducible transcription factors. The basic structure of nuclear receptors involves the n - terminal transactivation domain and c - terminal ligand binding domain. Transactivation domain that is DNA binding domain contains highly conserved zinc finger region whereas ligand binding domain is responsible for the transactivation within the targeted tissue. It has been reported that PPARγ, one of the nuclear receptor play an important role in mycobacterial infection. Mycobacterium tuberculosis is the bug that causes tuberculosis which is one of the deadly diseases of humankind. This bacterium gains entry through air passage and internalized by alveolar macrophages for efficient clearance. In spite of these barriers, bug has the tremendous ability to abrogate these responses for its own multiplication like inhibition of autophagy. Autophagy is one of the host defence mechanisms that have gained popularity in last 4 - 5 years for their anti-microbial responses.Various factors like ATP, Vitamin D and cytokines have been shown to induce autophagy. ATP is reported to induce autophagy by increasing intracellular calcium level. In our lab we are trying to study the response of one of the calcium ionophore that increases intracellular calcium level, Calcimycin in inducing autophagy in THP-1 cells. So, in this study we tried to link the role of calcimycin induced autophagy with the expression of another nuclear factor, HNF-4α.