Disease relevance of TSC22D3

• In contrast, GILZ production persists in tumor-infiltrating macrophages in Burkitt lymphomas [1].
• Activated macrophages in the granulomas of patients with Crohn disease or tuberculosis do not produce GILZ [1].
• The development of delayed-type hypersensitivity reactions is associated with the down-regulation of GILZ gene expression within lesions [1].

High impact information on TSC22D3

• In contrast, GILZ does not prevent CD40 ligand-mediated inhibition of phagocytosis, indicating that it affects some but not all aspects of DC maturation [2].
• IL-10, dexamethasone (DEX), and transforming growth factor (TGF)beta stimulate GILZ production in human immature DCs derived from monocytes and from CD34+ cells [2].
• GILZ prevents DCs from activating antigen-specific T lymphocyte responses [2].
• GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response [2].
• Administration of GCs to patients stimulates GILZ expression in their circulating antigen-presenting cells, and this contributes to the weak lymphocyte responses of GC-treated patients [2].

Biological context of TSC22D3

• GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis [3].
• GILZ overexpression protects CTLL-2 cells from IL-2 withdrawal-induced apoptosis, whereas cell death is accelerated in cells unable to express GILZ [3].
• Cloning, chromosomal assignment and tissue distribution of human GILZ, a glucocorticoid hormone-induced gene [4].
• A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells [5].
• Time-course experiments showed that in wild-type (WT) thymocytes GILZ up-regulation was followed by sequential Bcl-xL decreased expression and activation of caspase-8 and of caspase-3 [6].

Anatomical context of TSC22D3

• We found that GILZ was constitutively produced by macrophages in nonlymphoid tissues of humans and mice [1].
• In murine lymphocytes, glucocorticoids induce expression of glucocorticoid-induced leucine zipper (GILZ), which prevents the nuclear factor kappaB (NF-kappaB)-mediated activation of transcription [1].
• In contrast, the persistence of GILZ gene expression in macrophages infiltrating Burkitt lymphomas may contribute to the failure of the immune system to reject the tumor [1].
• Indeed, transient expression of GILZ in Jurkat T cells blocked induction of a reporter construct driven by the FasL promoter [7].
• Dexamethasone and IL-10 stimulate glucocorticoid-induced leucine zipper synthesis by human mast cells [8].

Associations of TSC22D3 with chemical compounds

• Our present results indicate that histamine, IL-4 and IL-5 alone or in combination with SCF do not downregulate GILZ production by MCs [8].
• Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia [9].
• The effect of GILZ on LPS-, IL-1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was assessed in BEAS-2B cells overexpressing GILZ [10].
• In addition, quantitative PCR shows that DEX down-regulates GR and up-regulates glucocorticoid-induced leucine zipper levels, whereas ICI 182,780 does not counteract these effects [11].
• To determine whether the in vitro outcomes could predict in vivo effects of GCs, 15 individuals underwent a 0.25-mg dexamethasone (DEX) suppression test (DST) while determining GILZ and IL-2 mRNA levels in their peripheral blood mononuclear cells incubated with hydrocortisone, DEX, budesonide, and prednisolone [12].

Other interactions of TSC22D3

• We also investigated whether GILZ production was modulated by (i) IL-10, because of its common immunosuppressive properties with GCs, (ii) histamine because of its pro-inflammatory properties and (iii) IL-4 and IL-5 because of their ability to favour MC survival and proliferation with SCF [8].
• Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ [9].
• Results indicate that GILZ inhibits both T-cell receptor (TCR)-induced interleukin-2/interleukin-2 receptor expression and NF-kappaB activity [13].
• We show that induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon [2].
• Deletion and domain swap experiments identified small, discreet positive and negative elements in A-Myb and c-Myb that were required for the regulation of specific genes, such as DHRS2, DSIPI, and mim-1 [14].

Analytical, diagnostic and therapeutic context of TSC22D3

• Thus, GILZ represents a glucocorticoid-induced gene product that can inhibit a variety of activation-induced events, at least in part by direct interference with AP-1, and is therefore a candidate for a mediator of glucocorticoid-induced immunosuppression [7].
• The expression of GILZ was evaluated by using RT-PCR, Western blotting or immunocytochemistry [8].
• A similar role of hDIP is partially confirmed by the results of an RT-PCR analysis, demonstrating the widespread distribution of the protein among different human tissues [15].
• METHODS: GILZ expression was assessed by means of PCR and immunoblotting in human epithelial cells at baseline and after stimulation with dexamethasone or cytokines (IL-1beta, TNF-alpha, and IFN-gamma) [10].
• Ectopic expression of GILZ, confirmed by western blotting, gave a 90% inhibition of promoter constructs in absence of dexamethasone [16].

References