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Apigenin inhibits PMA-induced expression of pro-inflammatory cytokines and AP-1 factors in A549 cells

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Abstract

Acute and chronic alveolar or bronchial inflammation is thought to be central to the pathogenesis of many respiratory disorders. Cytokines and granulocyte macrophage colony-stimulating factors (GM-CSF) play an important role in chronic inflammation. Activator protein-1 (AP-1) the superfamily of transcription factors is involved in proliferation, differentiation, apoptosis, and transformation including inflammation. Understanding the function and regulation of proinflammatory factors involved in inflammation may provide the novel therapeutic strategies in the treatment of inflammatory diseases. Our aim of the present study is to investigate the pro-inflammatory cytokines and pattern of AP-1 factors expressed during activation of lung adenocarcinoma A549 cells by Phorbol-12-myristate-13-acetate (PMA) and to understand the anti-inflammatory effect of apigenin. A549 cells were treated with and without PMA or apigenin, and the cell viability was assessed by MTT assay. Expressions of inflammatory mediators and different AP-1 factors were analyzed by semi-quantitative RT-PCR. IL-6 protein secreted was analyzed by ELISA, and expressions of IL-1β, c-Jun, and c-Fos proteins were analyzed by Western blotting. Activation of A549 cells by PMA, induced the expression of pro-inflammatory cytokine (IL-1β, IL-2, IL-6, IL-8, and TNF-α) mRNAs and secretion of IL-6 and the expression of specific AP-1 factors (c-Jun, c-Fos, and Fra-1). Treatment of cells with apigenin, significantly inhibited PMA-stimulated mRNA expression of above pro-inflammatory cytokines, AP-1 factors, cyclooxygenase-2, and secretion of IL-6 protein. Results suggested that the AP-1 factors may be involved in inflammation and apigenin has anti-inflammatory effect, which may be useful for therapeutic management of lung inflammatory diseases.

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Acknowledgments

The authors wish to express their gratitude to UGC for the financial support granted to Centre with Potential for Excellence in Particular Area (UGC-CPEPA) grant [8-2/2008(NS/PE)] and Department of Science and Technology-Promotion of University Research and Scientific Excellence (DST-PURSE), New Delhi [SR/59/Z-23/2010/38(c)] for financial support to Bangalore University, Bangalore. Authors also express their gratitude to UGC for BSR fellowship provided to Rajeshwari H Patil.

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Authors and Affiliations

  1. Department of Microbiology and Biotechnology, Bangalore University, Bangalore, 560 056, Karnataka, India

    Rajeshwari H. Patil, R. L. Babu, M. Naveen Kumar, K. M. Kiran Kumar, Shubha M. Hegde & S. Chidananda Sharma

  2. Department of Biology and Center for Biotechnology and Biomedical Sciences, Norfolk State University, Norfolk, VA, USA

    Govindarajan T. Ramesh

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  1. Rajeshwari H. Patil
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Correspondence to S. Chidananda Sharma.

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Patil, R.H., Babu, R.L., Naveen Kumar, M. et al. Apigenin inhibits PMA-induced expression of pro-inflammatory cytokines and AP-1 factors in A549 cells. Mol Cell Biochem 403, 95–106 (2015). https://doi.org/10.1007/s11010-015-2340-3

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