The Protein Product of the Tumor Suppressor Gene, Melanoma Differentiation-Associated Gene 7, Exhibits Immunostimulatory Activity and Is Designated IL-24

The melanoma differentiation-associated gene 7 (mda-7) has been studied primarily in the context of its tumor suppressor activity. Although mda-7 has been designated as IL-24 based on its gene location in the IL-10 locus and its mRNA expression in leukocytes, no functional evidence supporting this c...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-06, Vol.168 (12), p.6041-6046
Main Authors: Caudell, Eva G, Mumm, John B, Poindexter, Nancy, Ekmekcioglu, Suhendan, Mhashilkar, Abner M, Yang, Xiaohong Helena, Retter, Mark W, Hill, Paul, Chada, Sunil, Grimm, Elizabeth A
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - biosynthesis
Adjuvants, Immunologic - genetics
Adjuvants, Immunologic - metabolism
Adjuvants, Immunologic - physiology
CD3 Complex - analysis
Cell Division - immunology
Cell Line
Cytokines - antagonists & inhibitors
Cytokines - biosynthesis
Genes, Tumor Suppressor
Humans
Interleukin-10 - pharmacology
Interleukins - biosynthesis
Interleukins - genetics
Interleukins - metabolism
Interleukins - physiology
Leukocytes, Mononuclear - cytology
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
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Summary:The melanoma differentiation-associated gene 7 (mda-7) has been studied primarily in the context of its tumor suppressor activity. Although mda-7 has been designated as IL-24 based on its gene location in the IL-10 locus and its mRNA expression in leukocytes, no functional evidence supporting this cytokine designation exists. To further characterize MDA-7/IL-24 expression patterns in the human immune system, MDA-7/IL-24 protein levels were examined in human PBMC. MDA-7/IL-24 was detected in PHA- and LPS-stimulated whole PBMC lysate by Western blot and in PHA-activated CD56 and CD19 subsets by immunohistochemistry. The biological function of MDA-7/IL-24, secreted from Ad-MDA7-transfected HEK 293 cells, was assessed by examining the effect of MDA-7/IL-24 on the cytokine secretion profile of PBMC. Within 48 h MDA-7/IL-24 induced secretion of high levels of IL-6, TNF-alpha, and IFN-gamma and low levels of IL-1beta, IL-12, and GM-CSF from human PBMC as measured by ELISA. The MDA-7/IL-24-mediated induction of these Th1-type cytokines was inhibited by the addition of IL-10 to the PBMC cultures, suggesting that these two related protein family members may provide antagonistic functions. Therefore, because human blood leukocytes can be stimulated to produce MDA-7/IL-24, as well as respond to MDA-7/IL-24 by expressing secondary cytokines, MDA-7/IL-24 has the expression profile and major functional attributes that justify its designation as an IL.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.12.6041