Elsevier

Cellular Immunology

Volume 185, Issue 1, 10 April 1998, Pages 49-58
Cellular Immunology

Regular Article
Functional Consequences of the SHP-1 Defect in Motheaten Viable Mice: Role of NF-κB

https://doi.org/10.1006/cimm.1998.1272Get rights and content

Abstract

To define the functional consequences of the src-homology domain-1 protein (SHP-1) defect, we examined cytokine production and NF-κB activity in motheaten viable (Mev) mice. We found elevated levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and interferon-γ (IFN-γ) in Mev mice sera and cultured B and T cells compared to littermate control adult mice. The levels of interleukin-2 (IL-2) detected in Mev sera and activated Mev T cells were decreased, but IL-2 receptor expression was increased. We then evaluated the activity of NF-κB and found that this protein is highly expressed in Mev B and T cells. To determine if NF-κB had a role in causing the elevated levels of cytokines in Mev mice, we treated activated Mev T cells with an NF-κB decoy and found that cell culture treatment with the decoy resulted in significant reduction of the secretion of IL-6, GM-CSF, and TNF, but not IFN-γ. Therefore, our data show that Mev mice secrete elevated levels of inflammatory cytokines, which can be mediators in the development of the Mev clinical disorder, and that NF-κB has an important role in this process, impacting upon the regulation of the immune response.

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    To whom correspondence and reprint requests should be addressed at Department of Medicine, University of Florida, P.O. Box 100221, Gainesville, FL 32610. Fax: (352) 392-8483.

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