Pro-IL-16 regulation in activated murine CD4+ lymphocytes.

Abstract

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 G(0)/G(1) arrest by stabilizing the cyclin-dependent kinase inhibitor p27(Kip1). 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 p27(Kip1) 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.

• Authors: Fucheng Ren, Xin Zhan, Gregory Martens, Jinhee Lee, David Center, Sue Kim Hanson, Hardy Kornfeld
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 5 Pg. 2738-45 (Mar 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15728482 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-16
• Protein Precursors
• RNA, Messenger
• Calcineurin

Topics

• Animals
• CD4-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Calcineurin (physiology)
• Cell Cycle (genetics, immunology)
• Cell Proliferation
• Female
• Humans
• Interleukin-16 (biosynthesis, deficiency, metabolism, physiology)
• Lymphocyte Activation (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Protein Precursors (biosynthesis, deficiency, metabolism, physiology)
• RNA, Messenger (biosynthesis, metabolism)
• Resting Phase, Cell Cycle (genetics, immunology)
• Transfection