@article{438df9148eac4b2dbf73df7170942050,
title = "TNF-α induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway",
abstract = "Tpl2 knockout mice produce low levels of TNF-α when exposed to lipopolysaccharide (LPS) and they are resistant to LPS/D-Galactosamine-induced pathology. LPS stimulation of peritoneal macrophages from these mice did not activate MEK1, ERK1, and ERK2 but did activate JNK, p38 MAPK, and NF-κB. The block in ERK1 and ERK2 activation was causally linked to the defect in TNF-α induction by experiments showing that normal murine macrophages treated with the MEK inhibitor PD98059 exhibit a similar defect. Deletion of the AU-rich motif in the TNF-α mRNA minimized the effect of Tpl2 inactivation on the induction of TNF-α. Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport, of TNF-α mRNA from the nucleus to the cytoplasm.",
author = "Dumitru, {Calin D.} and Ceci, {Jeffrey D.} and Christos Tsatsanis and Dimitris Kontoyiannis and Konstantinos Stamatakis and Lin, {Jun Hsiang} and Christos Patriotis and Jenkins, {Nancy A.} and Copeland, {Neal G.} and George Kollias and Tsichlis, {Philip N.}",
note = "Funding Information: The authors wish to thank Dr. K. Hayakawa for help in measuring the antibody response to the T cell-dependent antigen KLH, Dr. G. Rall for measuring T cell cytotoxic responses to LCMV, and Dr. A. Klein-Szanto for help with the interpretation of histology. The authors also wish to thank Drs. E. Alnemri, S. Bear, T. Manser, and Y. Sykulev for critical review of the manuscript and Dr. T. O. Chan for helpful discussions. The work was supported by Public Health Service grant R01 CA38047 (to P. N. T.), by the National Cancer Institute (N. G. C.) and by the Hellenic General Secretariat of Research and Technology and EC grants QLG1-1999-00202 and QLK6-1999-02203 (to G. K.). C. P. was a special fellow of the Leukemia Society of America Inc. (now The Leukemia and Lymphoma Society).",
year = "2000",
month = dec,
day = "22",
doi = "10.1016/S0092-8674(00)00210-5",
language = "English (US)",
volume = "103",
pages = "1071--1083",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}