Interleukin-10

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Interleukin-10 2H24

Figure 1. IL-10 N-Terminus of helix A
Figure 1. IL-10 N-Terminus of helix A
Interleukin 10 is a ternary complex that requires specific assembly for proper function. The IL-10 complex is composed of IL-10,IL-10R1,IL-10R2. The initial step is the formation of IL-10 and IL-10R1 generating a conformational change that is required for IL-10R2 to be able to associate and form the ternary complex [1]. The completed complex activates the JAK/STAT signaling pathway.
Figure 2. Sequential assembly of the ternary complex
The completion of the ternary complex is dependent on the conformational changes that occur in the N-Terminus of the helix labelled A. The conformational changes occur when the cIL-10 binds with IL-10R1. There is a positional change of about 1 angstrom at residues between Cys-12 and Leu-46. Due to the











IL-10

Interleukin-10 is in the class cytokine.[1] Interleukin-10 is a very powerful anti-inflammatory cytokine that is most commonly found to be produce by moncytes [2]. IL-10 has the ability to be a immunosupressive as well as a anti-angiogenic this means that it has the ability both promot and inhibit tumors[3]. There are many types of cytokines that have many funtions such as from antiinflammatory cytokines,cytokine synthesis inhibitory factor and proinflammitory cytokines[4].

There are many interleukins that fall within the cytokine class such as IL-1,IL-2,IL-3,IL-4...IL-31,IL-32,IL-33,IL-3 and IL-35.

PDB ID 2h24

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2h24, resolution 2.00Å ()
Related: 1inr
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml


Interleukin-10 and Rheumatoid Arthritis

IL-10 is investigated for its role in patients with Rheumatoid Arthritis (RA) as well as those with Osteoarthritis (OA)[5]. RA is an autoimmune disorder that affects the synovial tissues via chronic synovitis. Chronic synovitis often results in joint destruction due to re-absorption of bone and the distruction of cartilage[6] [7]. IL-10 is found to spontaneously be produce in synovial tissue of patients with RA and OA but not in normal synovial tissue.The variation in secretion of IL-10 is thought to be at about 75% under the control of the genetics of the individual[8].When IL-10 is present there is a inhibition of the proinflammatory cytokines, namely TFN-α, IL-1α, IL-1β, IL-6, IL-8 [9].


Image:Illu_synovial_joint.jpg[10]


Shelly Huebert




References

  1. ↑ 1.0 1.1 Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem. 2006 Nov 17;281(46):35088-96. Epub 2006 Sep 18. PMID:16982608 doi:10.1074/jbc.M606791200
  2. ↑ Hudson LL, Rocca KM, Kuwana M, Pandey JP. Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses. Genes Immun. 2005 May;6(3):274-8. PMID:15772682
  3. ↑ Shih CM, Lee YL, Chiou HL, Hsu WF, Chen WE, Chou MC, Lin LY. The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer. 2005 Dec;50(3):291-7. Epub 2005 Aug 24. PMID:16122836 doi:10.1016/j.lungcan.2005.07.007
  4. ↑ Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med. 1994 May 1;179(5):1517-27. PMID:8163935
  5. ↑ Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med. 1994 May 1;179(5):1517-27. PMID:8163935
  6. ↑ Nemec P, Goldbergova MP, Gatterova J, Vasku A, Soucek M. Association of polymorphisms in interleukin-10 gene promoter with autoantibody production in patients with rheumatoid arthritis. Ann N Y Acad Sci. 2009 Sep;1173:501-8. PMID:19758192 doi:10.1111/j.1749-6632.2009.04625.x
  7. ↑ Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med. 1994 May 1;179(5):1517-27. PMID:8163935
  8. ↑ Nemec P, Goldbergova MP, Gatterova J, Vasku A, Soucek M. Association of polymorphisms in interleukin-10 gene promoter with autoantibody production in patients with rheumatoid arthritis. Ann N Y Acad Sci. 2009 Sep;1173:501-8. PMID:19758192 doi:10.1111/j.1749-6632.2009.04625.x
  9. ↑ de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209-20. PMID:1940799
  10. ↑ http://en.wikipedia.org/wiki/Synovial_membrane
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