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Tryptase activates isolated adult cardiac fibroblasts via protease activated receptor-2 (PAR-2)

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Protease activated receptor-2 (PAR-2) derived cycloxygenase-2 (COX-2) was recently implicated in a cardiac mast cell and fibroblast cross-talk signaling cascade mediating myocardial remodeling secondary to mechanical stress. We designed this study to investigate in vitro assays of isolated adult cardiac fibroblasts to determine whether binding of tryptase to the PAR-2 receptor on cardiac fibroblasts will lead to increased expression of COX-2 and subsequent formation of the arachodonic acid metabolite 15-d-Prostaglandin J2 (15-d-PGJ2). The effects of tryptase (100 mU) and co-incubation with PAR-2 inhibitor peptide sequence FSLLRY-NH2 (10-6M) on proliferation, hydroxyproline concentration, 15-d-PGJ2 formation and PAR-2/COX-2 expression were investigated in fibroblasts isolated from 9 week old SD rats. Tryptase induced a significant increase in fibroproliferation, hydroxyproline, 15-d-PGJ2 formation and PAR-2 expression which were markedly attenuated by FSLLRY. Tryptase-induced changes in cardiac fibroblast function utilize a PAR-2 dependent mechanism.

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Acknowledgments

We are grateful to Andrew Barnes and Rebecca Nolan for their technical assistance.

Disclosure

We have no conflicts of interest to declare in regards to relationships (inclusive of but not limited to, employment by an industrial concern, ownership of stock, membership on a standing advisory council or committee, being on the board of directors, or being publicly associated with the company or its products) with pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services related to the subject matter of this article.

Author contribution

DBM conceived of the study, and participated in its design and coordination, and performed the statistical analysis and drafted the manuscript. JM carried out the cell culture studies, immunohistochemistry and performed statistical analysis. JSJ was involved in drafting the manuscript or revising it critically for important intellectual content. All authors read and approved the final manuscript.

Funding sources

This study was supported by NIH Heart, Lung and Blood Institute Grant RO1-HL-62228 (jsj), University of South Carolina Magellan Award (dbm) and University of South Carolina Center of Biomedical Research Excellence (COBRE) Cardiovascular Diseases (dbm).

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Authors and Affiliations

  1. Department of Pharmacology, University of Mississippi School of Pharmacy, 311 Faser Hall, University, MS, 38677, USA

    David B. Murray & Krishna T. Nagalla

  2. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, 29208, USA

    Jennifer McLarty-Williams & Joseph S. Janicki

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  1. David B. Murray
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  2. Jennifer McLarty-Williams
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Correspondence to David B. Murray.

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Murray, D.B., McLarty-Williams, J., Nagalla, K.T. et al. Tryptase activates isolated adult cardiac fibroblasts via protease activated receptor-2 (PAR-2). J. Cell Commun. Signal. 6, 45–51 (2012). https://doi.org/10.1007/s12079-011-0146-y

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