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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Krishnan, S. Articles by Tsokos, G. C. Search for Related Content PubMed PubMed Citation Articles by Krishnan, S. Articles by Tsokos, G. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL CYCLOHEXIMIDE Medline Plus Health Information Lupus

Increased Caspase-3 Expression and Activity Contribute to Reduced CD3 Expression in Systemic Lupus Erythematosus T Cells¹

Sandeep Krishnan^*, Juliann G. Kiang^*,,, Carolyn U. Fisher^*, Madhusoodana P. Nambiar^,, Hang T. Nguyen^*,¶, Vasileios C. Kyttaris^*,||, Bhabadeb Chowdhury^*, Violeta Rus^# and George C. Tsokos^2,*,,¶

^* Department of Cellular Injury and Department of Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910; Department of Medicine and Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; ^¶ Rheumatology Service, Walter Reed Army Medical Center, Washington, D.C. 20307; ^|| Section of Rheumatology, Washington Hospital Center, Washington, D.C. 20010; and ^# Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201

T cells isolated from patients with systemic lupus erythematosus (SLE) express low levels of CD3-chain, a critical molecule involved in TCR-mediated signaling, but the involved mechanisms are not fully understood. In this study we examined caspase-3 as a candidate for cleaving CD3 in SLE T cells. We demonstrate that SLE T cells display increased expression and activity of caspase-3. Treatment of SLE T cells with the caspase-3 inhibitor Z-Asp-Glu-Val-Asp-FMK reduced proteolysis of CD3 and enhanced its expression. In addition, Z-Asp-Glu-Val-Asp-FMK treatment increased the association of CD3 with lipid rafts and simultaneously reversed the abnormal lipid raft preclustering, heightened TCR-induced calcium responses, and reduced the expression of FcR-chain exclusively in SLE T cells. We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3-chain and suggest that such molecules can be considered in the treatment of this disease.

This article has been cited by other articles:

				D. R. Fernandez, T. Telarico, E. Bonilla, Q. Li, S. Banerjee, F. A. Middleton, P. E. Phillips, M. K. Crow, S. Oess, W. Muller-Esterl, et al. Activation of Mammalian Target of Rapamycin Controls the Loss of TCR{zeta} in Lupus T Cells through HRES-1/Rab4-Regulated Lysosomal Degradation J. Immunol., February 15, 2009; 182(4): 2063 - 2073. [Abstract] [Full Text] [PDF]

				A. Das, M. Hoare, N. Davies, A. R. Lopes, C. Dunn, P. T.F. Kennedy, G. Alexander, H. Finney, A. Lawson, F. J. Plunkett, et al. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection J. Exp. Med., September 1, 2008; 205(9): 2111 - 2124. [Abstract] [Full Text] [PDF]

				Y.-T. Juang, Y. Wang, G. Jiang, H.-B. Peng, S. Ergin, M. Finnell, A. Magilavy, V. C. Kyttaris, and G. C. Tsokos PP2A Dephosphorylates Elf-1 and Determines the Expression of CD3{zeta} and FcR{gamma} in Human Systemic Lupus Erythematosus T Cells J. Immunol., September 1, 2008; 181(5): 3658 - 3664. [Abstract] [Full Text] [PDF]

				N. Mozaffarian, A. E. Wiedeman, and A. M. Stevens Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1 Rheumatology, September 1, 2008; 47(9): 1335 - 1341. [Abstract] [Full Text] [PDF]

				V. R. Moulton, V. C. Kyttaris, Y.-T. Juang, B. Chowdhury, and G. C. Tsokos The RNA-stabilizing Protein HuR Regulates the Expression of {zeta} Chain of the Human T Cell Receptor-associated CD3 Complex J. Biol. Chem., July 18, 2008; 283(29): 20037 - 20044. [Abstract] [Full Text] [PDF]

				E. C. Jury, J. Eldridge, D. A. Isenberg, and P. S. Kabouridis Agrin Signalling Contributes to Cell Activation and Is Overexpressed in T Lymphocytes from Lupus Patients J. Immunol., December 1, 2007; 179(11): 7975 - 7983. [Abstract] [Full Text] [PDF]

				J. C Crispin, V. Kyttaris, Y.-T. Juang, and G. C Tsokos Systemic lupus erythematosus: new molecular targets Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii65 - iii69. [Abstract] [Full Text] [PDF]

				B. Chowdhury, S. Krishnan, C. G. Tsokos, J. W. Robertson, C. U. Fisher, M. P. Nambiar, and G. C. Tsokos Stability and Translation of TCR {zeta} mRNA Are Regulated by the Adenosine-Uridine-Rich Elements in Splice-Deleted 3' Untranslated Region of {zeta}-Chain J. Immunol., December 1, 2006; 177(11): 8248 - 8257. [Abstract] [Full Text] [PDF]

				C. W. Thomson, W. A. Teft, W. Chen, B. P.-L. Lee, J. Madrenas, and L. Zhang FcR{gamma} Presence in TCR Complex of Double-Negative T Cells Is Critical for Their Regulatory Function J. Immunol., August 15, 2006; 177(4): 2250 - 2257. [Abstract] [Full Text] [PDF]