Pro-IL-16 regulation in activated murine CD4+ lymphocytes
| Autor: | Fucheng Ren, Xin Zhan, Gregory Martens, Jinhee Lee, David Center, Sue Kim Hanson, Hardy Kornfeld |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_treatment T cell Immunology Biology Lymphocyte Activation Transfection Resting Phase Cell Cycle TCIRG1 Interleukin 21 Mice medicine Immunology and Allergy Cytotoxic T cell Animals Humans RNA Messenger Protein Precursors Cell Proliferation Mice Knockout Messenger RNA Interleukin-16 Mice Inbred BALB C Kinase Calcineurin Cell Cycle Molecular biology Cell biology Mice Inbred C57BL Cytokine medicine.anatomical_structure Female |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 174(5) |
| ISSN: | 0022-1767 |
| Popis: | Prior DNA microarray studies suggested that IL-16 mRNA levels decrease following T cell activation, a property unique among cytokines. We examined pro-IL-16 mRNA and protein expression in resting and anti-CD3 mAb-activated primary murine CD4+ T cells. Consistent with the microarray reports, pro-IL-16 mRNA levels fell within 4 h of activation, and this response is inhibited by cyclosporin A. Total cellular pro-IL-16 protein also fell, reaching a nadir at 48 h. Pro-IL-16 comprises a C-terminal cytokine domain and an N-terminal prodomain that are cleaved by caspase-3. Pro-IL-16 expressed in transfected tumor cells was previously shown to translocate to the nucleus and to promote G0/G1 arrest by stabilizing the cyclin-dependent kinase inhibitor p27Kip1. In the present study, we observed increased S-phase kinase-associated protein 2 mRNA expression in IL-16 null mice, but basal expression and activation-dependent regulation of p27Kip1 were no different from wild-type mice. Stimulation with anti-CD3 mAb induced transiently greater thymidine incorporation in IL-16-deficient CD4+ T cells than wild-type controls, but there was no difference in cell survival or in the CFSE dilution profiles. Analysis of CD4+ T cell proliferation in vivo using BrdU labeling similarly failed to identify a hyperproliferative phenotype in T cells lacking IL-16. These data demonstrate that pro-IL-16 mRNA and protein expression are dynamically regulated during CD4+ T cell activation by a calcineurin-dependent mechanism, and that pro-IL-16 might influence T cell cycle regulation, although not in a dominant manner. |
| Databáze: | OpenAIRE |
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