Disease relevance of IL19

• It remains to be clarified whether IL-19 and IL-20 are implicated in the pathogenesis of psoriasis [1].
• We conclude that pANCA occurs not only in humans but also in IL19(-/-) mice with colitis and likely represents a cross-reactivity with enteric bacterial antigens [2].
• IL-23-dependent epidermal hyperplasia was observed in IL-19(-/-) and IL-24(-/-) mice, but was inhibited in IL-20R2(-/-) mice [3].

High impact information on IL19

• IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis [3].
• IL-19 shares a receptor complex with IL-20, indicating that the biological activities of these two cytokines overlap and that both may play an important role in regulating development and proper functioning of the skin [4].
• Unlike IL-10, which forms an intercalated dimer, the molecule of IL-19 is a monomer made of seven amphipathic helices, A-G, creating a unique helical bundle [4].
• Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types [5].
• These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles [6].

Chemical compound and disease context of IL19

• During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis [7].

Biological context of IL19

• In addition, GM-CSF was capable of directly inducing IL-19 gene expression in monocytes [8].
• The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA [8].
• Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass [9].
• DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP) in IL19 and IL20 and two SNPs in IL10 [10].
• Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis [11].

Anatomical context of IL19

• IL-19 and IL-20 were found to be preferentially expressed in monocytes [12].
• The expression of IL-19 and 20 mRNA was confined to the basal and suprabasal keratinocytes [1].
• Maturation of dendritic cells from human PBMC in the presence of IL-19 resulted in an increase in IL-10 levels within these cells, whereas IL-12 was not affected [13].
• A2B Adenosine Receptors Induce IL-19 from Bronchial Epithelial Cells, Resulting in TNF-{alpha} Increase [14].
• The amount of IL-19 released from HBEC was sufficient to activate a human monocytic cell line (THP-1) and increase the release of TNF-alpha [14].

Associations of IL19 with chemical compounds

• Treatment with cyclosporine A and calcipotriol resulted in disappearance of the IL-19 and 20 mRNA [1].
• Hence, these data indicate that NECA increases the release of IL-19 from HBECs via activation of A(2B) receptors, and IL-19 in turn activates human monocytes to release TNF-alpha, which upregulates A(2B) receptor expression in HBECs [14].

Physical interactions of IL19

• As evident fromB andC an extended interaction surface is created in the IL-19/IL-20R1 and IFN-gamma/receptor complexes by the interaction of this structural element with a long loop of the respective receptor[15]

Regulatory relationships of IL19

• In vitro experiments showed that IL-6 and TNF-alpha upregulated IL-19 protein expression in monocytes [9].
• Furthermore, in whole PBMC cultures, IL-19 up-regulated IL-4 and down-regulated IFNgamma in a dose-dependent manner [16].

Other interactions of IL19

• We report here identification and cloning of a gene and corresponding cDNAs encoding a novel homologue of IL-10, designated IL-19 [8].
• IL-19 does not bind or signal through the canonical IL-10 receptor complex, suggesting existence of an IL-19 specific receptor complex, the identity of which remains to be discovered [8].
• Arrows denote the location of helix B and the corresponding structural elements in IL-19 and IFN-gamma as well as the location of receptor loop L2 [15].
• In addition, mda-7 and IL-20, but not IL-19, bind to another receptor complex, composed by IL-22R and DIRS1/IL20Rbeta (type II IL-20R) [5].
• The objectives of this study were to document the expression of IL-19 and IL-20, localize their expression in human fetal membranes and to examine their influence on the production of other inflammatory cytokines (IL-1, IL-6, IL-8, and TNF-alpha) from placental membranes.Methods [17].

Analytical, diagnostic and therapeutic context of IL19

• Using in situ hybridization we have studied mRNA expression of IL-19, 20, and 24 and their related receptor chains in skin from psoriatic patients before and during short-term treatment with either oral cyclosporine A or topical calcipotriol [1].
• IL-20, IL-19, IL-20Ralpha, IL-20Rbeta and IL-22Ralpha mRNA expression were determined by quantitative reverse transcriptase-polymerase chain reaction [7].
• Next, we developed monoclonal and polyclonal antibodies to measure the levels of IL-19 in the sera of patients with psoriasis and healthy volunteers using an enzyme-linked immunosorbent assay [18].
• The expression of IL-19 and IL-20 was studied by reverse transcriptase polymerase chain reaction (RT-PCR) and localized using immunohistochemistry [17].
• There was a statistically significant difference between MDA 1 and MDA 2 levels (p < 0.01), each of which were also significantly different from the MDA levels of control group (p < 0.001 and p < 0.01, respectively) [19].

References