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Changes in cytosol and membrane TNF inhibitory protein‐B1 levels associated with protection from TNF‐induced cytotoxicity
Author(s) -
Henn Alicia D.,
Berleth Erica S.,
Mihich Enrico,
Ehrke M. Jane
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0543fje
Subject(s) - cytosol , cycloheximide , tumor necrosis factor alpha , cytotoxicity , chemistry , apoptosis , necrosis , endogeny , cytotoxic t cell , microbiology and biotechnology , biochemistry , biology , immunology , medicine , protein biosynthesis , in vitro , enzyme
Tumor necrosis factor‐α (TNF) at low, noncytotoxic concentrations induces factors that protect cells against cytotoxic concentrations of TNF alone or in combination with cycloheximide (CHX). We have found that cells pretreated with TNF inhibitory protein‐B1 (TIP‐B1), a novel protein isolated in our laboratory from the cytosol of TNF‐treated cells, are protected from TNF‐ induced cell death. Immunocytochemical analyses and subcellular fractionation indicated that in untreated normal human dermal fibroblasts (NHDF), endogenous TIP‐B1 is located in the cytosol and at the plasma membrane. During pretreatment of NHDF with protection‐inducing concentrations of TNF, transient changes in cytosolic and membrane TIP‐B1 levels occur. These changes occur before and coincident with the onset of TNF‐protective activity, which is then sustained as TIP‐B1 levels return toward baseline. During pretreatment, TIP‐B1 mRNA levels increased only marginally (1.6‐fold) and with kinetics different from that of the protein. The results suggest that changes in TIP‐B1 levels at specific sites may trigger the production or activation of secondary protective factors and that these changes in TIP‐B1 levels may not be transcriptionally regulated.