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 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.
Caudell
Eva G
EG
Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Mumm
John B
JB
Poindexter
Nancy
N
Ekmekcioglu
Suhendan
S
Mhashilkar
Abner M
AM
Yang
Xiaohong Helena
XH
Retter
Mark W
MW
Hill
Paul
P
Chada
Sunil
S
Grimm
Elizabeth A
EA
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017252:CD3 Complex / Q000032:analysis; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016147:Genes, Tumor Suppressor; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D000099180:Interleukin-24
D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D016207:Cytokines; D016753:Interleukin-10; D007378:Interleukins; D000099180:Interleukin-24