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

• Published in: Cellular immunology 1998-04, Vol.185 (1), p.49-58
• Main Authors: Khaled, Annette R., Butfiloski, Edward J., Sobel, Eric S., Schiffenbauer, Joel
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - secretion; Binding, Competitive; Cells, Cultured; Cytokines - blood; Cytokines - drug effects; Cytokines - secretion; Inflammation - blood; Inflammation - immunology; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-kappa B - physiology; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - deficiency; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - physiology; SH2 Domain-Containing Protein Tyrosine Phosphatases; src Homology Domains - genetics; src Homology Domains - immunology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - secretion
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1998.1272

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.