Published online before print August 11, 2003

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: jlb.0603254v1 74/5/932    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weber, N. C. Articles by Kiemer, A. K. Search for Related Content PubMed PubMed Citation Articles by Weber, N. C. Articles by Kiemer, A. K.

(Journal of Leukocyte Biology. 2003;74:932-941.)
© 2003 by Society for Leukocyte Biology

ANP inhibits TNF--induced endothelial MCP-1 expression—involvement of p38 MAPK and MKP-1

Nina C. Weber^*, Signe B. Blumenthal^*, Thomas Hartung, Angelika M. Vollmar^* and Alexandra K. Kiemer^*,1

^* Department of Pharmacy, Center of Drug Research, University of Munich, Germany; and
Institute of Biochemical Pharmacology, University of Konstanz, Germany

¹Correspondence: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037.

Atrial natriuretic peptide (ANP) has been shown to reduce tumor necrosis factor- (TNF-)-induced activation of endothelial cells via inhibition of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-B pathways. The aim of this study was to determine whether ANP is able to inhibit TNF--induced expression of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells and to elucidate the mechanisms involved. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ANP significantly reduced TNF--induced expression of MCP-1 protein and mRNA. The effects of ANP were shown to be mediated via the guanylyl-cyclase (GC)-coupled A receptor. Activation of the other GC-coupled receptor (natriuretic peptide receptor-B) by the C-type natriuretic peptide as well as activation of soluble GC with S-nitroso-L-glutathione (GSNO) exerted similar effects as ANP, supporting a role for cyclic guanosine monophosphate (cGMP) in the signal transduction. Antisense experiments showed a requirement of MAPK phosphatase-1 (MKP-1) induction and therefore, inhibition of p38 MAPK in the ANP-mediated inhibition of TNF--induced expression of MCP-1. To investigate a potential interplay between TNF--induced activation of p38 MAPK and NF-B, the p38 MAPK inhibitor SB203580 and a dominant-negative p38 MAPK mutant were used. The results indicated that the blockade of p38 MAPK activity leads to an increased activation of NF-B and therefore, suggest a counter-regulatory action of p38 MAPK and NF-B. As antisense experiments revealed a pivotal role for MKP-1 induction and therefore, p38 MAPK inhibition in ANP-mediated attenuation of MCP-1 expression, this action seems to be rather independent of NF-B inhibition.

Key Words: natriuretic peptides • endothelial cells • chemokines • cytokines • inflammation • atherosclerosis

This article has been cited by other articles:

				D. Yang, P. Xie, S. Guo, and H. Li Induction of MAPK phosphatase-1 by hypothermia inhibits TNF-{alpha}-induced endothelial barrier dysfunction and apoptosis Cardiovasc Res, February 1, 2010; 85(3): 520 - 529. [Abstract] [Full Text] [PDF]

				X. Palomer, D. Alvarez-Guardia, R. Rodriguez-Calvo, T. Coll, J. C. Laguna, M. M. Davidson, T. O. Chan, A. M. Feldman, and M. Vazquez-Carrera TNF-{alpha} reduces PGC-1{alpha} expression through NF-{kappa}B and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model Cardiovasc Res, March 1, 2009; 81(4): 703 - 712. [Abstract] [Full Text] [PDF]

				A. M. Whetzel, D. T. Bolick, and C. C. Hedrick Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3 Am J Physiol Cell Physiol, February 1, 2009; 296(2): C339 - C345. [Abstract] [Full Text] [PDF]

				R. Furst, M. F. Bubik, P. Bihari, B. A. Mayer, A. G. Khandoga, F. Hoffmann, M. Rehberg, F. Krombach, S. Zahler, and A. M. Vollmar Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo Mol. Pharmacol., July 1, 2008; 74(1): 1 - 8. [Abstract] [Full Text] [PDF]

				C. M. Kinney, U. M. Chandrasekharan, L. Mavrakis, and P. E. DiCorleto VEGF and thrombin induce MKP-1 through distinct signaling pathways: role for MKP-1 in endothelial cell migration Am J Physiol Cell Physiol, January 1, 2008; 294(1): C241 - C250. [Abstract] [Full Text] [PDF]

				T. J. Wang, M. G. Larson, M. J. Keyes, D. Levy, E. J. Benjamin, and R. S. Vasan Association of Plasma Natriuretic Peptide Levels With Metabolic Risk Factors in Ambulatory Individuals Circulation, March 20, 2007; 115(11): 1345 - 1353. [Abstract] [Full Text] [PDF]

				R. Furst, T. Schroeder, H. M. Eilken, M. F. Bubik, A. K. Kiemer, S. Zahler, and A. M. Vollmar MAPK phosphatase-1 represents a novel anti-inflammatory target of glucocorticoids in the human endothelium FASEB J, January 1, 2007; 21(1): 74 - 80. [Abstract] [Full Text] [PDF]

				A. Clerico, F. A. Recchia, C. Passino, and M. Emdin Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H17 - H29. [Abstract] [Full Text] [PDF]

				R. Furst, C. Brueckl, W. M. Kuebler, S. Zahler, F. Krotz, A. Gorlach, A. M. Vollmar, and A. K. Kiemer Atrial Natriuretic Peptide Induces Mitogen-Activated Protein Kinase Phosphatase-1 in Human Endothelial Cells via Rac1 and NAD(P)H Oxidase/Nox2-Activation Circ. Res., January 7, 2005; 96(1): 43 - 53. [Abstract] [Full Text] [PDF]