HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 6, 3030-3039, February 10, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/6/3030    most recent M506665200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Figueiredo, K. A. Articles by Cox, M. E. Search for Related Content PubMed PubMed Citation Articles by Figueiredo, K. A. Articles by Cox, M. E. Social Bookmarking                      What's this?

Relaxin Stimulates Leukocyte Adhesion and Migration through a Relaxin Receptor LGR7-dependent Mechanism^*

Kevin A. Figueiredo, Alice L. Mui^¶, Colleen C. Nelson^¶, and Michael E. Cox^¶1

From the Genetics Program and ^¶Department of Surgery, University of British Columbia and The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada

Leukocytes are critical effectors of inflammation and tumor biology. Chemokine-like factors produced by such inflammatory sites are key mediators of tumor growth that activate leukocytic recruitment and tumor infiltration and suppress immune surveillance. Here we report that the endocrine peptide hormone, relaxin, is a regulator of leukocyte biology with properties important in recruitment to sites of inflammation. This study uses the human monocytic cell line THP-1 and normal human peripheral blood mononuclear cells to define a novel role for relaxin in regulation of leukocyte adhesion and migration. Our studies indicate that relaxin promotes adenylate cyclase activation, substrate adhesion, and migratory capacity of mononuclear leukocytes through a relaxin receptor LGR7-dependent mechanism. Relaxin-stimulated cAMP accumulation was observed to occur primarily in non-adherent cells. Relaxin stimulation results in increased substrate adhesion and increased migratory activity of leukocytes. In addition, relaxin-stimulated substrate adhesion resulted in enhanced chemotaxis to monocyte chemoattractant protein-1. These responses in THP-1 and peripheral blood mononuclear cells are relaxin dose-dependent and proportional to cAMP accumulation. We further demonstrate that LGR7 is critical for mediating these biological responses by use of RNA interference lentiviral short hairpin constructs. In summary, we provide evidence that relaxin is a novel leukocyte stimulatory agent with properties affecting adhesion and chemomigration.

Received for publication, June 20, 2005 , and in revised form, October 20, 2005.

^* This work was supported by operating grants from the National Cancer Institute of Canada and fellowship support from the Canadian Prostate Cancer Research Initiative (to K. A. F.) and the Michael Smith Foundation for Health Research (to M. E. C. and C. C. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

¹ To whom correspondence should be addressed: The Prostate Centre, Vancouver General Hospital, 2660 Oak St, Vancouver BC, V6H 3Z6, Canada. Tel.: 604-875-4818; Fax: 604-875-5654; E-mail: michael.cox{at}vch.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Simon and A. Einspanier The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus) Reproduction, March 1, 2009; 137(3): 517 - 525. [Abstract] [Full Text] [PDF]

				K. Santora, C. Rasa, D. Visco, B. G. Steinetz, and C. A. Bagnell Antiarthritic Effects of Relaxin, in Combination with Estrogen, in Rat Adjuvant-Induced Arthritis J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 887 - 893. [Abstract] [Full Text] [PDF]

				T.-Y. Ho, W. Yan, and C. A. Bagnell Relaxin-induced matrix metalloproteinase-9 expression is associated with activation of the NF-{kappa}B pathway in human THP-1 cells J. Leukoc. Biol., May 1, 2007; 81(5): 1303 - 1310. [Abstract] [Full Text] [PDF]

				M. J. Lorenowicz, J. van Gils, M. de Boer, P. L. Hordijk, and M. Fernandez-Borja Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis J. Leukoc. Biol., December 1, 2006; 80(6): 1542 - 1552. [Abstract] [Full Text] [PDF]