Disease relevance of IL13

• In order to achieve specific targeting of the IL13R in gliomas, we have mutagenized human (h) IL13 [1].
• Our results suggest that a spectrum of human carcinomas express binding sites for IL13 [2].
• Association between severe respiratory syncytial virus infection and IL13/IL4 haplotypes [3].
• The IL4 -509 T allele and IL13 +2044 A allele carriers less often had purpura than the corresponding non-carriers [4].
• We have recently documented that the vast majority of patients with glioblastoma multiforme (GBM) over-express a receptor (R) for interleukin 13 (IL13) in situ [5].

Psychiatry related information on IL13

• Arg110Gln has been suggested to lead to enhanced IL-13 signaling and thus may be involved in shifting the immune reaction towards the hyper-reactivity characteristic for the sowda form, thereby promoting defense mechanisms [6].
• Working memory deficits in multiple sclerosis: a controlled study with auditory P600 correlates [7].
• These findings may indicate that auditory hallucinations in schizophrenia are associated with impaired synchronization of the processes related to target detection, as reflected by the P600 [8].
• Additionally, the P600 might serve as a valuable investigative tool for a more comprehensive understanding of the neurobiological substrate of drug abuse [9].
• Abnormal P600 in obsessive-compulsive disorder. A comparison with healthy controls [10].
• An IL13 polymorphism in the promoter region may modulate the adverse effects of cigarette smoking on pulmonary function in long-term cigarette smokers [11].

High impact information on IL13

• IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-beta and promotes epithelial damage, mucus production, and eosinophilia [12].
• Injured cells produce adenosine that enhances IL-13 production [12].
• Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth [13].
• Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix [13].
• By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes [13].

Chemical compound and disease context of IL13

• In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia [14].
• A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4 [2].
• Induction of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene transcription in human breast cancer cell lines and in normal mammary epithelial cells by interleukin-4 and interleukin-13 [15].
• Tyrosine phosphorylation of IRS-I was also induced by insulin and insulin-like growth factor I. Sublines of colorectal carcinoma cells unresponsive to growth modulation by IL-4, IL-13 or insulin-like growth factor I-induced growth did not phosphorylate IRS-1 [16].
• Exposure of ZR-75-1 breast cancer cells to IL-4 or IL-13 for 10 days decreased the amplitude of the mitogenic action of 17 beta-estradiol by 75% and 55%, respectively, while these cytokines failed to change basal cell proliferation [17].

Biological context of IL13

• Ten single-nucleotide polymorphisms (SNPs), including two promoter SNPs in the IL4R locus on chromosome 16p11, one promoter SNP in the IL4 locus on chromosome 5q31, and four SNPs--including two promoter SNPs--in the IL13 locus on chromosome 5q31 were examined for association, linkage disequilibrium, and interaction [18].
• Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure [19].
• Interleukin 13 (IL13) belongs to a family of cytokines whose members exhibit structural homology, despite amino acid sequence dissimilarity [20].
• For example, while of limited sequence homology, IL13 and IL4 share a signaling receptor, IL13/4 receptor, on a variety of human normal cells [20].
• OBJECTIVE: We sought to determine whether the related palindromic elements from IL4, IL5, and IL13 also act as enhancers of gene transcription [21].

Anatomical context of IL13

• In the search for genes involved in type 1 diabetes (T1D), other than the well-established risk alleles at the human leukocyte antigen loci, we have investigated the association and interaction of polymorphisms in genes involved in the IL4/IL13 pathway in a sample of 90 Filipino patients with T1D and 94 controls [18].
• Interestingly, IL13-1112T had opposite transcriptional effects in nonpolarized CD4(+) T cells, paralleled by distinct patterns of DNA-protein interactions at the IL13 promoter [22].
• Recently, we have demonstrated that human (h) glioma cell lines express large number of receptors (R) for interleukin 13 (IL13) (Debinski, W., Obiri, N. I., Powers, S. K., Pastan, I., and Puri, R. K. (1995) Clin. Cancer Res. 1, 1253-1258) [23].
• Using in vivo, in vitro, and in silico analysis, we show that the IL13-1112T allele enhanced IL13 promoter activity in primary human and murine CD4(+) Th2 lymphocytes [22].
• For increased plasma total IgE concentration, the best 2-locus model consisted of R130Q in IL13 and C-431T in the thymus and activation-regulated chemokine gene (TARC) [24].

Associations of IL13 with chemical compounds

• RESULTS: The latex allergy phenotype was significantly associated with promoter polymorphisms in IL13 -1055 (P = 0.02), IL18 -607 (P = 0.02), and IL18 -656 (P = 0.02) compared with nonatopic controls [25].
• DNA was extracted from blood collected in EDTA tubes, and polymorphisms at positions 50 and 551 of the IL4 receptor, position 110 of IL13 and position 181 of the high-affinity IgE receptor were investigated by sequence-specific PCR or direct sequencing [26].
• Recombinant IL-13 protein inhibits inflammatory cytokine production induced by lipopolysaccharide in human peripheral blood monocytes [27].
• PGE2 was more efficacious than beta-agonist in activating PKA and inhibiting cytokine production. beta-agonist and PGE2 also inhibited phorbol myristate acetate (PMA) + calcimycin-stimulated IFN-gamma and IL-2 (but not IL-13) production, suggesting that upstream CD3-initiated signaling is not the sole locus of PKA actions [28].
• IL-4 and IL-13 enhanced A23187-stimulated LTB(4) synthesis and increased mRNA expression and protein synthesis of LTA(4) hydrolase, but not those of cPLA(2) or 5-LO [29].
• We observed a significant association between responsiveness to montelukast and IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms [30].

Physical interactions of IL13

• IL-13 Induced the same complexes as IL-4, a finding explained by our studies implicating IL-4R as a shared component of the receptors [31].
• We have cloned a cDNA encoding an IL-13 binding protein (IL-13R) from the Caki-1 human renal carcinoma cell line [32].
• Activation of signal transducer and activator of transcription (STAT) 6 by IL-13 was confirmed by nuclear protein binding to a DNA probe derived from the eotaxin promoter [33].
• All sections of non-malignant brain tissues examined showed avid binding by the TfR with lack of consistent and specific binding of 125I-IL13 or -EGF [5].
• Co-expression of the cloned cDNA with that of IL-4R alpha resulted in a receptor complex that displayed high affinity for IL-13 (Kd approximately 30 pM), and that allowed cross-competition of IL-13 and IL-4 [34].

Enzymatic interactions of IL13

• We show that JAK2 kinase is rapidly phosphorylated and activated in response to IL-13 [35].
• Immunoprecipitation studies reveal that endothelial IL-4R alpha is rapidly tyrosine phosphorylated upon treatment with IL-13 and IL-4 [36].
• Antibody-mediated neutralization of IL-13 resulted in significant decreases in both cellular proliferation and levels of phosphorylated STAT6 of HL cell lines [37].
• In IGROV-1 cells, Tyk2 was constitutively phosphorylated and this phosphorylation was augmented by IL-4 or IL-13 [38].

Regulatory relationships of IL13

• IL-13-induced IgG4 and IgE synthesis is IL-4-independent, since it was not affected by neutralizing anti-IL-4 monoclonal antibody [39].
• The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway [40].
• Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis [41].
• Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15 [42].
• In vitro exposure to IL-13 of human umbilical vein EC induced surface expression of vascular cell adhesion molecule-1 (VCAM-1) [43].
• These results demonstrate that LPA induces IL-13Ralpha2 expression and release via PLD and JNK/AP-1 signal transduction and that pretreatment with LPA down-regulates IL-13 signaling in HBEpCs [44].

Other interactions of IL13

• The above results demonstrate that IL-4 and IL-13 share a receptor component that is important for signal transduction [45].
• A significant gene-gene interaction between S478P in IL4RA and the -1111 promoter variation in IL13, previously shown to be associated with BHR (P=.003), was detected [19].
• Thus, IL-13 elicits a spectrum of responses in vascular endothelium remarkably similar to that of IL-4 and IL-10 [43].
• IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation [40].
• In the process of screening T-cell lines for T helper 1 (Th1) and Th2 cytokine mRNAs, we observed that interleukin-13 (IL-13) mRNA was highly expressed in HTLV-1-infected, IL-2-dependent T-cell lines [46].

Analytical, diagnostic and therapeutic context of IL13

• RESULTS: Th-2 cytokines: IL-5 and IL13 expression increased before and during acute rejection, and decreased after successful antirejection therapy [47].
• Serum samples were collected from all patients before each infusion and assayed for IL18, IL12, and IL13 by enzyme linked immunosorbent assay (ELISA); IL18 was also measured eight weeks after the last infusion [48].
• Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13 [14].
• Here we report the discovery by molecular cloning of a new interleukin (interleukin-13 or IL-13) expressed in activated human T lymphocytes [27].
• The amino acid sequences of IL-4 and IL-13 are approximately 30% homologous and circular dichroism (CD) spectroscopy shows that both proteins have a highly alpha-helical structure [45].

References