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Angiotensin II bi-directionally regulates cyclooxygenase-2 expression in intestinal epithelial cells

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Abstract

We previously demonstrated that angiotensin II (Ang II) receptor signaling is involved in azoxymethane-induced mouse colon tumorigenesis. In order to clarify the role of Ang II in COX-2 expression in the intestinal epithelium, the receptor subtype-specific effect on COX-2 expression in a rat intestinal epithelial cell line (RIE-1) has been investigated. Ang II dose- and time-dependently increased the expression of COX-2, but not COX-1 mRNA and protein. This stimulation was completely blocked by the AT1 receptor antagonist but not the AT2 receptor antagonist. Ang II and lipopolysaccharide (LPS) additively induced COX-2 protein in RIE-1 cells, whereas the LPS-induced COX-2 expression was significantly attenuated by low concentrations of Ang II or the AT2 agonistic peptide CGP-42112A only in AT2 over-expressed cells. These data indicate that Ang II bi-directionally regulates COX-2 expression via both AT1 and AT2 receptors. Control of COX-2 expression through Ang II signaling may have significance in cytokine-induced COX-2 induction and colon tumorigenesis.

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Acknowledgements

The authors thank Dr. Raymond DuBois (Department of Medicine, Vanderbilt University) for sharing rat intestinal epithelial cell line. We are grateful to Ms. Lara. Pickel (Department of Engineering/Anatomy & Physiology, Kansas State University) for critical reading and constructive comments during the preparation of the manuscript. This work was supported in part by NIH grants RO3 CA091428, P50 CA90949, P30 CA68485, Kansas State University (KSU) Provost’s Fund and KSU College of Veterinary Medicine Dean’s Fund.

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  1. Department of Biochemistry, Vanderbilt University, School of Medicine, Nashville, TN, 37232, USA

    Tatsuo Tani, Tetsuo Takagi, Tsutomu Kanehira & Masaaki Tamura

  2. Department of Anatomy & Physiology, Kansas State University College of Veterinary Medicine, 210 Coles Hall, Manhattan, KS, 66506, USA

    Rie Ayuzawa, Dharmendra Kumar Maurya & Masaaki Tamura

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  1. Tatsuo Tani
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Correspondence to Masaaki Tamura.

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Tani, T., Ayuzawa, R., Takagi, T. et al. Angiotensin II bi-directionally regulates cyclooxygenase-2 expression in intestinal epithelial cells. Mol Cell Biochem 315, 185–193 (2008). https://doi.org/10.1007/s11010-008-9806-5

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