Part:BBa_K554004

IL10

IL-10 is an anti-inflammatory interleukin, produced mainly by monocytes. It is responsible for down-regulating the synthesis of pro-inflammatory cytokines like IFN-γ, IL-2, IL-3, TNFα (Th1 cytokines), class II MHC, and co-stimulatory molecules on macrophages. IL-10 also displays potent abilities to suppress the antigen presentation capacity of APCs (Antigen Presenting Cells), and it is also responsible for enhancing B cell survival, proliferation and antibody secretion. In this scenario IL-10 favors Th2 response (Elenkov & Chrousos, 1999).

Some studies suggested that IL-10 acts as immunoregulator in intestinal tract. For example Steidler et al (2000) used a genetically modified Lactococcus lacti expressing IL-10 to treat mice with Inflammatory Bowel Disease (IBD), and the inflammatory response signals were reduced in 50%. IBD is an autoimmune disease which, unlike the immune response found in intestinal tract due to stress, involves a Th1 polarization and inflammation.

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  COMPATIBLE WITH RFC[25]
• 1000
  COMPATIBLE WITH RFC[1000]

Usage and Biology

This part is used by [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil UNICAMP-EMSE Brazil team] as the final product of the [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil/Project#Device_2:_NO_sensor.2FIL-10_producer NO sensor device/ IL-10 producer] ("Device 2", which senses NO levels and responds by producing and secreting IL-10. This part is shown as green in the following schema:

The team chooses IL-10 to impair inflammatory response mediated by Th1 overstimulation (due to Device 1 action), to reach an equilibrium between immune stimulation (Th1) and suppression (Th2).

In the folllowing schema you can have a more detailed view of the [http://2011.igem.org/Team:UNICAMP-EMSE_Brazil/Project#Device_2:_NO_sensor.2FIL-10_producer NO sensor device/ IL-10 producer] ("Device 2") functioning:

Three-dimensional structure representation

You can find below a tridimensional structure of Homo sapiens IL-10 protein (retrieved from PDB 2h24, Yoon et al. 2006), solved by X-Ray crystallography at 2.0Å. This is a jmol applet, in which you can interactively see the protein format:

References

1. Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science 289. 2000. 1352–1355. [http://www.ncbi.nlm.nih.gov/pubmed/10958782 Link to Pubmed]
2. Yoon, S.I., Logsdon, N.J., Sheikh, F., Donnelly, R.P., Walter, M.R. Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. Journal: (2006) J.Biol.Chem. 281: 35088-35096 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16982608 Link to PubMed]
3. Elenkov IJ, Chrousos GP. Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease. Trends Endocrinol Metab. 1999 Nov;10(9):359-368. [http://www.ncbi.nlm.nih.gov/pubmed/10511695 Link to Pubmed ]