Positive and negative regulation of interleukin-12 gene expression.
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.
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The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
Riemann
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Gri
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Trinchieri
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D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*
D018664:Interleukin-12