POSITIVE AND NEGATIVE REGULATION OF INTERLEUKIN-12 GENE-EXPRESSION

Interleukin-12: (IL-12) is a pivotal cytokine representing the link be tween the cellular and humoral branches of an effective host immune de fense apparatus, IL-12 is a heterodimer produced by phagocytic, B, den dritic, and possibly other accessory cells in both innate and adaptive immnne responses. It is a key factor in the induction of T cell-depen dent and independent activation of macrophages, generation of T helper type 1 (Th1) and cytotoxic T cells, suppression of IgG1 and IgE produ ction, induction of organ-specific autoimmunity, and resistance to bac terial and parasitic infections [I], IL-12 has a powerful anti-tumor a nd anti-metastatic activity against many murine tumors [2-5] as well a s human tumors [6-17]. The genes encoding the two heterologous chains of IL-12, p40 and p35 are located on different human chromosomes, Toge ther, p40 and p35 form the biologically active IL-12, Their expression s are highly cordinated 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, respective ly, A transient or irreversible dysregulation of IL-12 production may reflect a pathogen/tumor cell-induced disruption in the highly coordin ated expression of p40 and p35, The understanding of the molecular mec hanisms governing the expression of IL-12 p40 and p35 genes in the con text of interactions between pathogens and the immune system is essent ial in efforts aimed at designing therapeutic strategies to treat infe ctious and malignant diseases.