Disease relevance of IL11

• A polymorphism in the IL11 gene is associated with ulcerative colitis [1].
• However, prevention of bacterial infections by antibiotic treatment, although it delayed death, was ineffective in promoting survival either in placebo-treated and IL11-treated mice [2].
• Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF [3].
• In agreement with the pleiotropic effects of IL-11 on different hematopoietic lineages and bone cells, IL-11 receptor transcripts were found to be expressed by the myelogenous leukemia cell line K562, the megakaryocytic leukemia cell line Mo7E, the erythroleukemia cell line TF1, and the osteosarcoma cell lines MG-63 and Saos-2 [4].
• In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL-11 alone or when combined with other cytokines [3].

Psychiatry related information on IL11

• The effect of administering recombinant human interleukin 11 in conjunction with cytotoxic insults to the gastrointestinal tract has been studied using the crypt microcolony assay for stem cell function and whole-animal survival time studies [5].

High impact information on IL11

• The production of interleukin-6 by stromal osteoblastic cells, as well as the responsiveness of bone marrow cells to cytokines such as interleukin-6 and interleukin-11, is regulated by sex steroids [6].
• The development of osteoclasts from their progenitors is dependent on stromal-osteoblastic cells, which are a major source of cytokines that are critical in osteoclastogenesis, such as interleukin-6 and interleukin-11 [6].
• Expression of RANKL mRNA in osteoblasts/stromal cells is up-regulated by osteotropic factors such as 1 alpha, 25(OH)2D3, PTH, and IL-11 [7].
• The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures [8].
• It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11 [9].

Chemical compound and disease context of IL11

• Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid [10].
• In contrast, IL-4 only weakly stimulated, and IL-7, hepatocyte growth factor, and herpes simplex virus Type 2 did not stimulate, IL-11 production [10].
• Effect of azacytidine in the release of leukemia inhibitory factor, oncostatin m, interleukin (IL)-6, and IL-11 by mononuclear cells of patients with refractory anemia [11].
• Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis [12].
• Synergistic effects of interleukin-11 with other growth factors on the expansion of hematopoietic progenitors from normal individuals and chronic myeloid leukemia patients resistant to treatment with cytosine arabinoside or eilatin [13].

Biological context of IL11

• Several potential transcriptional control sequences that may play an important role in the control of IL11 gene expression have been identified within the 5'-flanking region of the human IL11 gene [14].
• The human IL11 genomic sequence is 7 kb in length and consists of five exons and four introns [14].
• To evaluate the role of the IL11 gene in IBD, two polymorphisms, including a dinucleotide repeat in the promoter region, have been genotyped in 222 patients with CD, 152 patients with ulcerative colitis (UC) and 400 healthy controls [1].
• Altered expression of IL11 appears to be involved in the genetic predisposition of UC [1].
• The genomic sequence of human interleukin-11 (IL11) has been isolated based on its sequence homology with a cDNA clone encoding primate IL11 [14].

Anatomical context of IL11

• When IL11 was administered, only a slight improvement in the hematopoietic status (both blood cell counts and progenitor cells) was observed after an 8-Gy exposure, and no improvement in hematopoietic reconstitution was observed after 9 Gy total-body irradiation [2].
• Similarly, IL11 in combination with bone marrow transplantation enhanced survival after 15 Gy 137Cs gamma rays [2].
• Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130 [15].
• We examined IL-11 production by primary osteoblasts and the effects of rat monoclonal anti-mouse glycoprotein 130 (gp130) antibody on osteoclast formation, using a coculture of mouse osteoblasts and bone marrow cells [8].
• Addition of IL-11, but not TPO, to NKCM-containing cultures resulted in further augmentation of polyploidy, with the generation of 50% to 70% polyploid megakaryocytes with a modal ploidy of 16N [16].

Associations of IL11 with chemical compounds

• The combination of IL-11 and dexamethasone yielded a magnitude of stimulation which was more similar to the combination of LIF and dexamethasone than IL-6 and dexamethasone [17].
• We also determined whether retinoic acid (RA) altered this IL-11 production [10].
• Compared with the control group, the quantitative level of L. monocytogenes in hepatic and splenic tissue was unchanged by rhIL-11 but was significantly increased by TNF or IL-11 inhibition [18].
• However, we were unable to show that JAK1 is tyrosine phosphorylated and activated by IL-11 under identical conditions [19].
• IL-11 acts on cells expressing gp130 and the IL-11 receptor (IL-11R) alpha-subunit (IL-11Ralpha) [20].

Physical interactions of IL11

• In vitro immunoprecipitation experiments showed that sIL11Ralpha specifically binds IL-11 and that binding is enhanced by gp130 [21].
• In contrast, the blocking monoclonal antibody B-R6, which recognized the gp80/IL-6 binding subunit failed to interfere with the IL-11 proliferative signal in the TF1 cell line [22].
• These results suggest that the IL-11 binding component is different from the gp80/IL-6 receptor [22].

Regulatory relationships of IL11

• We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995) [23].
• Detailed analysis with several patient samples further revealed that SF and IL-11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth [3].
• It did, however, inhibit rIL-1-stimulated and synergistically augment TGF-beta-stimulated IL-11 production [10].
• We further show that the in vitro kinase activity of JAK2 is greatly enhanced following stimulation with IL-11 in 3T3-L1 cells and TF-1 cells [19].
• Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity [24].
• IL11 has antisense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding RNAs with sense Alu elements, and Pol-III transcribed Alus [25].

Other interactions of IL11

• In contrast, IL-6 does not further enhance the effect of IL-11 [3].
• Within the hematopoietic system, the effects of IL-11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF) [3].
• Thus, IL-1, TGF-beta, and RSV stimulate epithelial-like cell IL-11 production, and RA regulates these inductive processes in a stimulus-specific fashion [10].
• Similarly, we also characterized two additional antibodies B-P8 and B-P4, which inhibited the TF1 cell proliferation observed in the presence of CNTF and IL-11, respectively [26].
• Here we identify a 130-kilodalton tyrosine-phosphorylated protein induced by IL-11 in 3T3-L1 cells as JAK2 tyrosine kinase [19].

Analytical, diagnostic and therapeutic context of IL11

• The IL11 gene has been localized to the long arm of human chromosome 19 at band 19q13.3-q13.4 by in situ hybridization [14].
• IL11 administered for 5 consecutive days beginning 2 h after total-body irradiation with 8 or 9 Gy 60Co gamma rays resulted in a significant increase in 30-day survival [2].
• Minimal basal IL-11 expression was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in NFb, AFb, HUVEC and HAEC [27].
• Phorbol myristate acetate (PMA) induced a twofold greater increase in IL-11 mRNA expression in neonatal fibroblasts (NFb) compared with adult fibroblasts (AFb), and a 3.6-fold greater increase in HUVEC than human adult aorta endothelial cells (HAEC) by Northern blot analysis [27].
• Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11 [4].

References