The effects of calpain inhibition upon IL-2 and CD25 expression in human peripheral blood mononuclear cells.
Calcium is an important contributor to T cell activation; it is also the major factor in the activation of the calcium-activated neutral proteinase, calpain. For this reason, we wanted to investigate if calpain has a role in T cell activation and what aspects of this activation calpain affects. As measured by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), calpain inhibition decreased interleukin-2 (IL-2) and CD25 mRNA expression in a dose-dependent manner, at early time points following the initial activation, and over extended periods of time in activated human peripheral blood mononuclear cells (PBMCs). Using an enzyme-linked immuno-sorbent assay (ELISA) specific for human IL-2, we found that calpain inhibition decreased IL-2 secretion in a dose-dependent manner, shortly after activation, and continuously over time. Inhibiting calpain caused a dose-dependent inhibition of CD25 cell surface expression and also inhibited expression shortly after activation and for at least 48 h. This study showed that calpain has an integral role in the synthesis of the two important T cell activation factors, IL-2 and CD25.
Schaecher
K E
KE
Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, Suite 310, Charleston, SC 29425, USA.
Goust
J M
JM
Banik
N L
NL
D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics*; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002154:Calpain; D007376:Interleukin-2; D037181:Lectins, C-Type; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens