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The synergistic induction of cyclooxygenase-2 in lung fibroblasts by angiotensin II and pro-inflammatory cytokines

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Abstract

Although we have demonstrated that Angiotensin II (Ang II) signaling plays a role in colon and lung tumorigenesis, the precise mechanisms by which Ang II stimulates tumorigenesis remain unclear. The aim of this study was to investigate the synergistic induction of COX-2 by Ang II and pro-inflammatory cytokines in lung fibroblasts. We also compared the efficiencies of Ang II-dependent COX-2 induction in lung epithelial cells and stromal cells. Ang II induced COX-2 expression in lung fibroblasts in a dose-dependent manner (10−9 to 10−7 M) through the Ang II subtype 1 receptor (AT1). In addition, Ang II synergistically stimulated the induction of COX-2 by pro-inflammatory cytokines, IL-1β, or TNF-α. Our results indicate that the pro-tumorigenic function of Ang II is attributable, in part, to its strong stimulatory effect of COX-2 expression in lung fibroblasts in which synergistic stimulation with pro-inflammatory cytokines was evident. It is also suggested that the AT1 receptor in lung fibroblasts may be a rational target for chemoprevention of lung cancer.

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Acknowledgments

The authors thank Dr. Dharmendra Maurya, Ms. Jennifer Reischman, and Marla Pyle (Department of Anatomy & Physiology, Kansas State University, Manhattan, KS) for critical reading and constructive comments during the preparation of the manuscript. This work was supported in part by Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, KSU Provost’s fund, KSU College of Veterinary Medicine Dean’s fund, NIH grant P20 RR017686.

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  1. Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, KS, USA

    Takaya Matsuzuka, Kathryn Miller, Lara Pickel, Chiyo Doi, Rie Ayuzawa & Masaaki Tamura

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  1. Takaya Matsuzuka
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  2. Kathryn Miller
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Correspondence to Masaaki Tamura.

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Matsuzuka, T., Miller, K., Pickel, L. et al. The synergistic induction of cyclooxygenase-2 in lung fibroblasts by angiotensin II and pro-inflammatory cytokines. Mol Cell Biochem 320, 163–171 (2009). https://doi.org/10.1007/s11010-008-9918-y

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  • DOI: https://doi.org/10.1007/s11010-008-9918-y

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