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Insight into the Anti-Inflammatory Mechanism of Action of Atrial Natriuretic Peptide, a Heart Derived Peptide Hormone: Involvement of COX-2, MMPs, and NF-kB Pathways

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Abstract

We sought to determine the in vivo anti-inflammatory activity of atrial natriuretic peptide (ANP) using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute and chronic skin inflammatory mice model. ANP treatment (2 μg/kg body weight/day/i.p. for acute and 0.5 μg/kg body weight/day/i.p. for chronic inflammatory study) was started after 30 min of TPA application. The standard drug, aspirin (ASP) (20 μg/kg body weight/day/i.p.; 10 μg/kg body weight/day/i.p., respectively) was used as a positive control for the both acute and chronic study. TPA alone treated mice exhibited a marked increase in the ear length (7 ± 0.08 vs. 13 ± 0.7 mm, p < 0.001) as well as in ear weight (80 ± 1.3 vs. 130 ± 1.5 mg, p < 0.001) as compared with control mice. Upon treatment with ANP, the increased ear length and weight were reverted back to near normal level. Similarly, ANP treatment markedly suppressed the TPA-induced chronic skin inflammatory lesion (5.7 ± 0.2 vs. 0.95 ± 0.05, p < 0.001) as compared with TPA-induced mouse skin. TPA-induced alterations in the levels of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total white blood cell (TWBC), serum tumor necrosis factor-α (TNF-α), natriuretic peptide receptor-A (NPR-A), cyclooxygenase-2 (COX-2), matrix metalloproteinase-2/-9 (MMP-2/-9) and nuclear factor kappa B (NF-κB) (p < 0.01, respectively) were reverted back to near normal levels. The results of the present study clearly show the in vivo anti-inflammatory activity of ANP, which is comparable with that of a standard drug, ASP. Our results suggest that ANP elicits its anti-inflammatory activity by down-regulating the expressions of NPR-A, COX-2, MMPs and NF-κB.

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Acknowledgments

Dr. EV wishes to thank the Indian Council of Medical Research (ICMR), and Department of Biotechnology (DBT), India for the financial support in the form of research project.

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    1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, India

      Lakshmi Priya Kalaiarasu, Vimala Subramanian, Boopathi Sowndharrajan & Elangovan Vellaichamy

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    Lakshmi Priya Kalaiarasu and Vimala Subramanian contributed equally to this work.

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    Kalaiarasu, L.P., Subramanian, V., Sowndharrajan, B. et al. Insight into the Anti-Inflammatory Mechanism of Action of Atrial Natriuretic Peptide, a Heart Derived Peptide Hormone: Involvement of COX-2, MMPs, and NF-kB Pathways. Int J Pept Res Ther 22, 451–463 (2016). https://doi.org/10.1007/s10989-016-9525-9

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