Interleukin 11

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IL11
Human IL-11 crystal structure.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL11, AGIF, IL-11, interleukin 11
External IDs OMIM: 147681 MGI: 107613 HomoloGene: 535 GeneCards: IL11
RNA expression pattern
PBB GE IL11 206924 at fs.png

PBB GE IL11 206926 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001267718
NM_000641

NM_008350
NM_001290423

RefSeq (protein)

NP_000632
NP_001254647

NP_001277352
NP_032376

Location (UCSC) Chr 19: 55.36 – 55.37 Mb Chr 7: 4.77 – 4.78 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Interleukin 11 (IL-11) is a protein that in humans is encoded by the IL11 gene.[3]

IL-11 is a multifunctional cytokine first isolated in 1990 from bone marrow-derived stromal cells. It is a key regulator of multiple events in hematopoiesis, most notably the stimulation of megakaryocyte maturation.[4] It is also known under the names adipogenesis inhibitory factor (AGIF)[5] and oprelvekin.

The human IL-11 gene, consisting of 5 exons and 4 introns, is located on chromosome 19,[3] and encodes a 23 kDa protein. IL-11 is a member of the IL-6-type cytokine family, distinguished based on their use of the common co-receptor gp130. Signal specificity is provided by the IL-11Rα subunit.

Downstream signalling[edit]

Signal transduction is initiated upon binding of IL-11 to IL-11Ralpha and gp130, facilitating the homodimerization of gp130 molecules. This permits gp130-associated Janus kinases (JAK) to become activated and phosphorylate intracellular tyrosine residues on gp130.[6]

Function[edit]

IL-11 has been demonstrated to improve platelet recovery after chemotherapy-induced thrombocytopenia, induce acute phase proteins, modulate antigen-antibody responses, participate in the regulation of bone cell proliferation and differentiation IL-11 causes bone-resorption. It stimulates the growth of certain lymphocytes and, in the murine model, stimulates an increase in the cortical thickness and strength of long bones. In addition to having lymphopoietic/hematopoietic and osteotrophic properties, it has functions in many other tissues, including the brain, gut, testis and bone.[7]

As a signaling molecule, interleukin 11 has a variety of functions associated with its receptor interleukin 11 receptor alpha; such functions include placentation and to some extent of decidualization.[8] IL11 has been expressed to have a role during implantation of the blastocyst in the endometrium of the uterus; as the blastocyst is imbedded within the endometrium, the extravillous trophoblasts will invade the maternal spiral arteries for stability and the transfer of essential life-sustaining elements via the maternal and fetal circulatory systems. This process is highly regulated due to detrimental consequences that can arise from aberrations of the placentation process: poor infiltration of the trophoblasts may result in preeclampsia while severely invasive trophoblasts may resolve in placenta accreta, increta or percreta; all defects which most likely would result in the early demise of the embryo and/or negative effects upon the mother.[8] IL11 has been shown to be present in the decidua and chorionic villi to regulate the extent in which the placenta implants itself; regulations to ensure the well-being of the mother but also the normal growth and survival of the fetus. A murine knockout model has been produced for this particular gene, with initial studies involving IL11 role in bone pathologies but have since progressed to fertility research; further research utilizes endometrial and gestational tissue from humans.[8][9]

Medical use[edit]

Interleukin 11 is manufactured using recombinant DNA technology and is marketed as a protein therapeutic called oprelvekin, for the prevention of severe thrombocytopenia in cancer patients.[10]

Research[edit]

Many IL-11 functions associated with cell growth and differentiation suggest a role for this cytokine in cancer. A number of studies reported IL-11 as a possible cancer progression marker suggesting that therapeutic targeting of IL-11 or IL11RA in humans may be beneficial, however as of 2017 clinically relevant IL-11 signalling antagonists were still under development.[11]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b McKinley D, Wu Q, Yang-Feng T, Yang YC (1992). "Genomic sequence and chromosomal location of human interleukin-11 gene (IL11)". Genomics. 13 (3): 814–9. PMID 1386338. doi:10.1016/0888-7543(92)90158-O. 
  4. ^ Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O'Hara RM, Leary AC, Sibley B, Clark SC, Williams DA (1990). "Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine". Proc. Natl. Acad. Sci. U.S.A. 87 (19): 7512–6. PMC 54777Freely accessible. PMID 2145578. doi:10.1073/pnas.87.19.7512. 
  5. ^ Kawashima I, Ohsumi J, Mita-Honjo K, Shimoda-Takano K, Ishikawa H, Sakakibara S, Miyadai K, Takiguchi Y (1991). "Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11". FEBS Lett. 283 (2): 199–202. PMID 1828438. doi:10.1016/0014-5793(91)80587-S. 
  6. ^ Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (August 2003). "Principles of interleukin (IL)-6-type cytokine signalling and its regulation". Biochem. J. 374 (Pt 1): 1–20. PMC 1223585Freely accessible. PMID 12773095. doi:10.1042/BJ20030407. 
  7. ^ Sims NA, Jenkins BJ, Nakamura A, Quinn JM, Li R, Gillespie MT, Ernst M, Robb L, Martin TJ (July 2005). "Interleukin-11 receptor signaling is required for normal bone remodeling.". Journal of Bone and Mineral Research. 20 (7): 1093–102. PMID 15940362. doi:10.1359/JBMR.050209. 
  8. ^ a b c Paiva P, Salamonsen LA, Manuelpillai U, Walker C, Tapia A, Wallace EM, Dimitriadis E (November 2007). "Interleukin-11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation". Endocrinology. 148 (11): 5566–72. PMID 17702845. doi:10.1210/en.2007-0517. 
  9. ^ Chen HF, Lin CY, Chao KH, Wu MY, Yang YS, Ho HN (May 2002). "Defective production of interleukin-11 by decidua and chorionic villi in human anembryonic pregnancy". J. Clin. Endocrinol. Metab. 87 (5): 2320–8. PMID 11994383. doi:10.1210/jc.87.5.2320. 
  10. ^ Neumega
  11. ^ Korneev, KV; Atretkhany, KN; Drutskaya, MS; Grivennikov, SI; Kuprash, DV; Nedospasov, SA (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis.". Cytokine. 89: 127–135. PMID 26854213. doi:10.1016/j.cyto.2016.01.021. 

Further reading[edit]