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Functional Role of Kallikrein 6 in Regulating Immune Cell Survival

Title: Functional Role of Kallikrein 6 in Regulating Immune Cell Survival.
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Name(s): Scarisbrick, Isobel, author
Epstein, Benjamin, author
Cloud, Beth, author
Yoon, Hyesook, 1975-, author
Wu, Jianmin, author
Renner, Danielle, author
Blaber, Sachiko, author
Blaber, Michael, author
Vandell, Alexander, author
Bryson, Alexandra, author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2011
Physical Form: computer
Physical Form: online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: BACKGROUND: Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the possible mechanism by which this may occur. METHODOLOGY/PRINCIPAL FINDINGS: Using murine whole splenocyte preparations and the human Jurkat T cell line we demonstrate that KLK6 robustly supports cell survival across a range of cell death paradigms. Recombinant KLK6 was shown to significantly reduce cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Moreover, KLK6-over expression in Jurkat T cells was shown to generate parallel pro-survival effects. In mixed splenocyte populations the vigorous immune cell survival promoting effects of KLK6 were shown to include both T and B lymphocytes, to occur with as little as 5 minutes of treatment, and to involve up regulation of the pro-survival protein B-cell lymphoma-extra large (Bcl-XL), and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim). The ability of KLK6 to promote survival of splenic T cells was also shown to be absent in cell preparations derived from PAR1 deficient mice. CONCLUSION/SIGNIFICANCE: KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. These findings point to a novel molecular mechanism regulating lymphocyte survival that is likely to have relevance to a range of immunological responses that depend on apoptosis for immune clearance and maintenance of homeostasis.
Identifier: FSU_migr_biomed_faculty_publications-0022 (IID), 10.1371/journal.pone.0018376 (DOI)
Keywords: kallikreins, lymphocytes, multiple sclerosis, cell death, cell survival
Uncontrolled subjects: Animals, B-Lymphocytes, Cell Death, Cell Proliferation, Cell Survival, Humans, Jurkat Cells, Kallikreins, Lymphocytes, Mice, Poly(ADP-ribose) Polymerases, Proto-Oncogene Proteins c-bcl-2, Receptor, PAR-1, Signal Transduction, Spleen, T-Lymphocytes
Note: Originally published in PLoS One.
Citation: Scarisbrick, I.A., Epstein, B., Cloud, B., Yoon, H., Wu, J., Blaber, S.I., Blaber, M., Vandell, A.G. and Bryson, A. (2011). Functional role of Kallikrein 6 in regulating immune cell survival. PLoS ONE 6(3): e18376. doi:10.1371/journal.pone.0018376.
Subject(s): Biochemistry
Biophysics
Molecular biology
Cytology
Developmental biology
Clinical biochemistry
Medical sciences
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0022
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: PLoS One.
Issue: 3, 6

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Scarisbrick, I., Epstein, B., Cloud, B., Yoon, H., Wu, J., Renner, D., … Bryson, A. (2011). Functional Role of Kallikrein 6 in Regulating Immune Cell Survival. Plos One. Retrieved from http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0022