Disease relevance of IL4I1

• Interleukin 4-induced gene 1 is activated in primary mediastinal large B-cell lymphoma [1].
• The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease [2].
• IL-4-induced immune deviation as antigen-specific therapy for inflammatory autoimmune disease [3].
• Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4+ subset in stimulated cultures [4].
• Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas [5].

High impact information on IL4I1

• An interleukin-4-induced transcription factor: IL-4 Stat [6].
• Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12 [2].
• Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis [7].
• These clones were also shown to strongly upregulated IL-4-induced germline epsilon RNA and formed dense aggregates with B cells [8].
• IL-4 induced a time- and dose-dependent increase of phosphocholine (pchol) with concomitant degradation of membrane PC (p < 0.05 compared with control) [9].

Chemical compound and disease context of IL4I1

• The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is dependent on JAK1 expression in human fibrosarcoma cells [10].
• Furthermore, infection of B cells by EBV introduced a relative resistance to the down-regulatory effects of DEX on IL-4-induced CD23 expression [11].
• These data suggest that the macrophage mannose receptor may be an essential participant in the mechanism of interleukin-4-induced macrophage fusion and implicate a novel function for this endocytic/phagocytic receptor in mediating foreign body giant cell formation at sites of chronic inflammation [12].
• Understanding IL-4-induced signaling leading to abnormal activation of AR will provide insights into the molecular mechanisms of androgen-independent progression of prostate cancer cells [13].
• Multiple signaling pathways mediate interleukin-4-induced 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene expression in human breast cancer cells [14].

Biological context of IL4I1

• CONCLUSION: Comparative genomics suggest that the promoter upstream of the NUP62 gene originally belonged to the IL4I1 gene and was later acquired by NUP62 via insertion of a retroposon [15].
• RESULTS: Here we provide evidence that the IL4I1 gene is specifically transcribed from the apparent promoter of the upstream NUP62 gene, and that the first two exons of NUP62 are also contained in the novel IL4I1_2 variant [15].
• FIG1 gene expression might be due to a constitutive activation of a cytokine signaling pathway in PMBL [1].
• Inhibition of antigen-specific T cell responses was associated with downregulation of constitutive, as well as interferon gamma- or IL-4-induced, class II MHC expression on monocytes by IL-10 and v-IL-10, resulting in the reduction in antigen-presenting capacity of these cells [16].
• Collectively these results indicate that mTNF-alpha, which is rapidly induced after activation of CD4+ T cells, participates in productive T-B cell interactions resulting in IL-4-induced Ig production [17].

Anatomical context of IL4I1

• While expression of IL4I1 driven from its previously described promoter is found mostly in B cells, the expression driven by the NUP62 promoter is restricted to cells in testis (Sertoli cells) and in the brain (e.g., Purkinje cells) [15].
• Interestingly, in human B-cell lines, FIG1 mRNA expression appeared restricted to the PMBL-derived MedB-1 and Karpas 1106 cell lines [1].
• Northern blot studies showed that FIG1 mRNA expression is mainly restricted to lymphoid tissues [1].
• A recombinant soluble form of the alpha subunit of the human high-affinity receptor for IgE (rsFc epsilon RI alpha), one of the potent IgE-binding molecules, was tested for its ability to regulate IL-4-induced IgE synthesis by human lymphocytes [18].
• Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells [19].

Associations of IL4I1 with chemical compounds

• The human FIG1 mRNA encodes a 567 amino acid protein that comprises a signal peptide and a large flavin-binding amino oxidase domain, and shares significant homology with secreted apoptosis-inducing L-amino acid oxidases [1].
• When compared to the LAAO crystal structure, hFig1 conserves key residues thought to be involved in catalysis and binding of the flavin adenine dinucleotide cofactor [20].
• This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment [19].
• In both the early and the late phase of the IL-4-induced response HC exerts its effects which are respectively IL-4 dependent and IL-4 independent [21].
• IL-4-induced expression of macrophage mannose receptor, which is a molecule pivotal to macrophage-mediated host defense, again appeared to be impaired in IBD monocytes [22].

Physical interactions of IL4I1

• Electrophoretic mobility shift assays using [32P]-labeled synthetic oligonucleotides encoding the consensus binding motif of activator protein-1 demonstrated that interleukin-4-induced binding of activator protein-1 composed of JunB was interfered by terfenadine [23].
• The Epstein-Barr virus-binding site on CD21 is involved in CD23 binding and interleukin-4-induced IgE and IgG4 production by human B cells [24].

Regulatory relationships of IL4I1

• In this study, we demonstrate that IL-4-induced STAT6 activation was inhibited profoundly by 24 h pretreatment with IFN-gamma in human primary airway epithelial cell cultures [25].
• Interleukin-2 inhibits the interleukin-4-induced human IgE and IgG4 secretion in vivo [26].
• Moreover, high SDF-1-expressing BMSSCs displayed an increased capacity for cellular growth and protection against interleukin-4-induced apoptosis [27].
• Interleukin-4-induced STAT6 recognizes and activates a target site in the promoter of the interleukin-4 receptor gene [28].
• p38 Mitogen-activated protein kinase regulates interleukin-4-induced gene expression by stimulating STAT6-mediated transcription [29].

Other interactions of IL4I1

• Expression of the IL4I1 gene from the "NUP62" promoter and the tissue specific involvement of the pre-mRNA processing machinery to regulate expression of two unrelated proteins indicate a novel mechanism of gene regulation [15].
• In contrast, CD40 mAb plus interleukin 4 induced the patients' B cells to synthesize IgE and to undergo deletional switch recombination [30].
• Jak1 expression is required for mediating interleukin-4-induced tyrosine phosphorylation of insulin receptor substrate and Stat6 signaling molecules [31].
• IFN-gamma also increased the rate of decay of IL-4-induced eotaxin-3 mRNA [25].
• Our data indicate that cells expressing the Val50/Pro478/Arg551 haplotype had significantly greater IL-13- or IL-4-induced TARC release than cells with other IL-4Ralpha genotypes [32].

Analytical, diagnostic and therapeutic context of IL4I1

• Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that all but one PMBL (16/17) displayed high FIG1 mRNA levels, whereas most NM-DLBLs (12/18) and all low-grade B-cell lymphomas tested (8/8) exhibited low FIG1 mRNA levels [1].
• Southern blot studies did not show rearrangement of the FIG1 gene [1].
• This conclusion was drawn on the basis of chemical cross-linking, immunoprecipitation, the ability of IL-13Ralpha' but not IL-13Ralpha to augment IL-4 binding affinity, and the requirement of IL-13Ralpha' for IL-4-induced STAT6 activation in Chinese hamster ovary (CHO) cells transfected with various receptor subunits [33].
• Subnanomolar concentrations of IL-4 induced a genistein-sensitive up-regulation of VCAM-1 in vascular cell cultures [34].
• In addition, the IL4-induced VCAM-1 expression was completely blocked by a single intravenous treatment of the isograft recipients with TNFR:Fc [35].

References