Regulation of soluble and surface-bound TRAIL in human T cells, B cells, and monocytes.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF/nerve growth factor superfamily that, apart from inducing cell death in susceptible cells, displays immunoregulatory functions influencing, for instance, T cell proliferation. It can be found in two forms: membrane-bound and soluble protein. The regulation of these is still not fully understood. In this study, we have analyzed the regulation of TRAIL surface expression and secretion in human T cells, B cells, and monocytes in response to specific stimuli. T cells, B cells, and monocytes were cultured in the presence of phytohemagglutinin (PHA)+interleukin (IL-2), anti-CD40+IL-4, and lipopolysaccharide (LPS), respectively. In particular, not only PHA+IL-2 but also LPS were able to induce secretion of soluble TRAIL, but did not enhance the expression of surface-bound TRAIL. Simultaneously, we investigated the effect of the pleiotropic stimulus interferon (IFN)-beta, known to target all leukocyte subsets, on TRAIL. Predominantly, monocytes were affected by IFN-beta, causing both release of soluble TRAIL and upregulation of the surface-bound form. IFN-beta, however, did not cause any upregulation of TRAIL in T cells. Our data serve as a basis to better understand the complex regulation of TRAIL in human peripheral immune cells and might help to clarify the role of the TRAIL system in immunopathology.
Ehrlich
Stefan
S
Institute of Neuroimmunology, Neuroscience Research Center, Charitè University Hospital, 10098 Berlin, Germany.
Infante-Duarte
Carmen
C
Seeger
Bibiane
B
Zipp
Frauke
F
D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D007155:Immunologic Factors; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta