| Involvement of calpain in the process of Jurkat T cell chemotaxis. | |
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MedLine Citation:
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PMID: 18831007 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Massive T cell infiltration into the central nervous system is a hallmark of multiple sclerosis (MS) and its rodent model experimental autoimmune encephalomyelitis (EAE), resulting in the induction of many of the pathophysiological events that lead to neuroinflammation and neurodegeneration. Thus, blocking T cell migration into the central nervous system may reduce disease severity in MS and EAE. One potential target for reducing T cell migration is inhibition of the Ca(2+)-activated neutral protease calpain. Previous studies in other cell types have demonstrated that migration is reduced by incubation of cells with calpain inhibitors. Thus, we hypothesize that calpain inhibition will reduce migration of T cells in response to and toward the chemokine CCL2. To test this hypothesis, the intracellular free Ca(2+) levels in Jurkat E6-1 T cells was first measured by the fura-2 assay to assess whether the intracellular ion environment would support calpain activation. The intracellular free Ca(2+) levels were found to increase in response to CCL2. The cells were next treated with the calpain inhibitor calpeptin in a multiwelled Boyden chamber with CCL2 used as the chemoattractant. These studies demonstrate that inhibition of calpain with its inhibitor calpeptin produces a dose-dependent inhibition of chemotaxis. Calpain activity, as measured by live cell imaging, was also increased in response to CCL2, providing further evidence of its involvement in the process of chemotaxis and migration. These studies provide evidence for the involvement of calpain in the mechanisms of chemotaxis and warrants further exploration in MS patient and EAE animal samples. |
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Authors:
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Jonathan T Butler; Supriti Samantaray; Craig C Beeson; Swapan K Ray; Naren L Banik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of neuroscience research Volume: 87 ISSN: 1097-4547 ISO Abbreviation: J. Neurosci. Res. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-03 Completed Date: 2009-03-31 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 7600111 Medline TA: J Neurosci Res Country: United States |
Other Details:
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Languages: eng Pagination: 626-35 Citation Subset: IM |
Copyright Information:
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(c) 2008 Wiley-Liss, Inc. |
Affiliation:
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Department of Molecular and Cellular Biology and Pathobiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Calcium
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metabolism Calpain / antagonists & inhibitors, metabolism* Chemokine CCL2 / pharmacology Chemotaxis, Leukocyte / physiology* Cysteine Proteinase Inhibitors / pharmacology Dipeptides / pharmacology Dose-Response Relationship, Drug Fura-2 Glycoproteins / pharmacology Humans Jurkat Cells Signal Transduction / physiology T-Lymphocytes / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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ES-12878/ES/NIEHS NIH HHS; NS-31622/NS/NINDS NIH HHS; NS-41088/NS/NINDS NIH HHS; NS-45967/NS/NINDS NIH HHS; NS-56176/NS/NINDS NIH HHS; NS-57811/NS/NINDS NIH HHS; R01 NS041088-06/NS/NINDS NIH HHS; R01 NS041088-07/NS/NINDS NIH HHS; R01 NS041088-08/NS/NINDS NIH HHS; R01 NS056176-03/NS/NINDS NIH HHS; R01 NS056176-04/NS/NINDS NIH HHS; R01 NS057811-02/NS/NINDS NIH HHS; R01 NS057811-03/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL2; 0/Cysteine Proteinase Inhibitors; 0/Dipeptides; 0/Glycoproteins; 0/calpain inhibitors; 117591-20-5/calpeptin; 7440-70-2/Calcium; 96314-98-6/Fura-2; EC 3.4.22.-/Calpain |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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