NYMC Faculty Publications

LPS Induces the Interaction of a Transcription Factor, LPS-Induced TNF-Alpha Factor, and STAT6(B) With Effects on Multiple Cytokines

Author Type(s)

Faculty

Additional Author Affiliation

Touro College of Dental Medicine at NYMC

DOI

10.1073/pnas.0501159102

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

First Page

5132

Last Page

5137

Document Type

Article

Publication Date

4-5-2005

Department

Pharmacology

Abstract

TNF-alpha is a pivotal cytokine whose overproduction can be lethal. Previously, we identified a transcription factor, LPS-induced TNF-alpha factor (LITAF), that regulates TNF-alpha transcription. We now report the discovery and characterization of a regulatory cofactor that we call signal transducer and activator of transcription (STAT) 6(B) because of its considerable homology to STAT6 [here referred to as STAT6(A)]. The STAT6(B) gene expression was found to be activated by LPS. Furthermore, we show that cotransfection of STAT6(B) and LITAF induces an interaction between the two proteins, consequently forming a complex that subsequently translocates into the nucleus and up-regulates the transcription of cytokines. The effect of the complex on a panel of cytokines was tested. In addition, the specific role of LITAF in this complex was established with experiments, including RNA interference technology. Overall, these findings describe roles for LITAF, STAT6(B), and the LITAF-STAT6(B) complex in the regulation of inflammatory cytokines in response to LPS stimulation in mammalian cells.

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