Disease relevance of Litaf

• Using these cells, we now show that LITAF expression can be induced after challenge either with LPS from Porphyromonas gingivalis via agonism at TLR-2, or with LPS from Escherichia coli via agonism at TLR-4, both requiring functional MyD88 [1].
• TBX1 is the major candidate gene for DiGeorge syndrome (DGS) [2].
• Thyroid dysgenesis related to Tbx1 inactivation may explain an overrepresentation of hypothyroidism occurring in patients with the 22q11DS [3].
• Using the growth delay assay, the therapeutic response was enhanced by prior TBX: for example, in mice receiving 3000 rad TBX 1 day before fibrosarcoma cell inoculation, the growth delay from 8 to 12 mm produced by CY (150 mg/kg) was 18.8 days compared with 9.4 days without prior TBX [4].

High impact information on Litaf

• We conclude that LITAF is an important mediator of the LPS-induced inflammatory response that can be distinguished from NF-kappaB pathway and that p38alpha is the specific kinase involved in the pathway linking LPS/MyD88/LITAF to TNF [1].
• Previously we identified a transcription factor, LPS-Induced TNF-alpha Factor (LITAF), mediating inflammatory cytokine expression in LPS-induced processes [1].
• To further identify LITAF signaling pathways, we tested mouse TLR-2(-/-), -4(-/-), and -9(-/-) and WT peritoneal macrophages exposed to LPS [1].
• Tbx1 is a transcription factor, the mutation of which is sufficient to cause most of the physical features of 22q11DS, but the gene had not been previously associated with the behavioral/psychiatric phenotype [5].
• The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning [3].

Biological context of Litaf

• Negative regulation of monocyte chemoattractant protein-1 gene expression by a mouse estrogen-enhanced transcript [6].
• Finally, macLITAF(-/-) macrophages rescued by LITAF cDNA transfection restored levels of TNF-alpha similar to those observed in WT cells [1].
• TBX1 is required for inner ear morphogenesis [7].
• We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1 [8].
• Of the more than 30 genes deleted in this syndrome, TBX1 is the only one that has been found to be mutated in some patients with a phenotype that is very similar to that of patients with the full deletion, suggesting that TBX1 haploinsufficiency is a major contributor to the syndrome's phenotype [9].

Anatomical context of Litaf

• Mouse estrogen enhanced transcript (mEET) is endogenously expressed in a mouse thymus epithelial cell line 1 (MTEC1) [10].
• SDF-1alpha production is negatively regulated by mouse estrogen enhanced transcript in a mouse thymus epithelial cell line [10].
• In normal development, this interaction may be facilitated by Tbx1-expressing mesenchyme filling the gap between the pharyngeal endoderm and the detached thyroid primordium [3].
• Finally, we show that Tbx1 in the mesoderm is required to sustain cell proliferation [11].
• In addition, these experiments revealed that different pharyngeal arches require Tbx1 in different tissues [11].

Associations of Litaf with chemical compounds

• Addition of 17 beta-estradiol (E2) to the MTEC1 cell cultures enhanced mEET mRNA expression and, meanwhile, significantly inhibited monocyte chemoattractant protein-1 (MCP-1) production [6].
• Dox-induced activation of the mEET gene profoundly inhibited MCP-1 expression at both mRNA and protein levels and alleviated its chemotactic activity [6].

Regulatory relationships of Litaf

• Moreover, we disclosed that mEET inhibited the production of SDF-1alpha by its suppression of NF-kappaB translocation into nucleus [10].

Other interactions of Litaf

• Conversely, inactivation of the mEET gene substantially augmented MCP-1 expression [6].
• Activation of the mEET gene markedly attenuated activity of nuclear NF-kappaB [6].

Analytical, diagnostic and therapeutic context of Litaf

• Northern blot analysis shows that mouse LITAF is already expressed at embryonic day 7 of development, and is highly expressed in adult liver, heart and kidney [12].
• Molecular cloning and characterization of mouse LITAF cDNA: role in the regulation of tumor necrosis factor-alpha (TNF-alpha) gene expression [12].
• Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy [13].

References