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Positive and negative regulation of interleukin-12 gene expression.

TitlePositive and negative regulation of interleukin-12 gene expression.
Publication TypeJournal Article
Year of Publication1998
AuthorsMa X, Riemann H, Gri G, Trinchieri G
JournalEur Cytokine Netw
Volume9
Issue3 Suppl
Pagination54-64
Date Published1998 Sep
ISSN1148-5493
KeywordsAnimals, Gene Expression Regulation, Humans, Immunity, Cellular, Interleukin-12
Abstract

Interleukin-12 (IL-12) is a pivotal cytokine representing the link between the cellular and humoral branches of an effective host immune defense apparatus. IL-12 is a heterodimer produced by phagocytic, B, dendritic, and possibly other accessory cells in both innate and adaptive immune responses. It is a key factor in the induction of T cell-dependent and independent activation of macrophages, generation of T helper type 1 (Th1) and cytotoxic T cells, suppression of IgG1 and IgE production, induction of organ-specific autoimmunity, and resistance to bacterial and parasitic infections [1]. IL-12 has a powerful anti-tumor and anti-metastatic activity against many murine tumors [2-5] as well as human tumors [6-17]. The genes encoding the two heterologous chains of IL-12, p40 and p35 are located on different human chromosomes. Together, p40 and p35 form the biologically active IL-12. Their expressions are highly coordinated during an effective immune response. However, under some pathological conditions, IL-12 is under- or overexpressed, resulting either in a lack of resistance to microbial infection and to uncontrolled tumor growth, or in destructive inflammation, respectively. A transient or irreversible dysregulation of IL-12 production may reflect a pathogen/tumor cell-induced disruption in the highly coordinated expression of p40 and p35. The understanding of the molecular mechanisms governing the expression of IL-12 p40 and p35 genes in the context of interactions between pathogens and the immune system is essential in efforts aimed at designing therapeutic strategies to treat infectious and malignant diseases.

Alternate JournalEur Cytokine Netw
PubMed ID9831187
Grant ListCA10815 / CA / NCI NIH HHS / United States
CA20833 / CA / NCI NIH HHS / United States
CA32898 / CA / NCI NIH HHS / United States

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