Sandbox Reserved 777: Difference between revisions

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== Introduction ==

Interleukin 10 (IL-10) belongs to a class of proteins called cytokines. Cytokines are chemical messengers that are produced by and act on cells of the immune system.<ref>National Institute of Allergy and Infectious Diseases, ”Immune Cells and their Products: Cytokines”. Web. 16Nov2013 <http://www.niaid.nih.gov/topics/immuneSystem/immuneCells/Pages/cytokines.aspx></ref> It is also part of the IL-10 family of cytokines, which also includes IL-19, IL-20, IL-22, IL-24 and IL-26. This grouping was made based on similarities in structure, function, and location of the encoding genes.<ref>Sabat, Robert. IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010; 21:315–324</ref> IL-10 has also previously been called cytokine synthesis inhibitory factor (CSIF) because of its anti-inflammatory properties and ability to inhibit the production of other cytokines.<ref>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; 174(5):1209-1220</ref> The ability to limit the immune response to pathogens is crucial to preventing self-inflicted damage to the host. This cytokine is expressed in many eukaryotic hosts, as well as some viruses. A quick protein BLAST of the human IL-10 sequence reveals homology with IL-10 of many other primate species, as well as that found in bats, horses, elephants, rodents, sheep, cats and birds. The remainder of this page will focus on human IL-10.

Interleukin 10 (IL-10) belongs to a class of proteins called cytokines. Cytokines are chemical messengers that are produced by and act on cells of the immune system.<ref>National Institute of Allergy and Infectious Diseases, ”Immune Cells and their Products: Cytokines”. Web. 16Nov2013 <http://www.niaid.nih.gov/topics/immuneSystem/immuneCells/Pages/cytokines.aspx></ref> It is also part of the IL-10 family of cytokines, which also includes IL-19, IL-20, IL-22, IL-24 and IL-26. This grouping was made based on similarities in structure, function, and location of the encoding genes.<ref name="sabat">Sabat, Robert. IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010; 21:315–324</ref> IL-10 has also previously been called cytokine synthesis inhibitory factor (CSIF) because of its anti-inflammatory properties and ability to inhibit the production of other cytokines.<ref>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; 174(5):1209-1220</ref> The ability to limit the immune response to pathogens is crucial to preventing self-inflicted damage to the host. This cytokine is expressed in many eukaryotic hosts, as well as some viruses. A quick protein BLAST of the human IL-10 sequence reveals homology with IL-10 of many other primate species, as well as that found in bats, horses, elephants, rodents, sheep, cats and birds. The remainder of this page will focus on human IL-10.

== Structure ==

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== Mechanism of Action ==

Most hematopoietic cells express the IL-10 transmembrane receptors, IL-10R1 and IL-10R2. While IL-10R1 is specific only for IL-10 cytokine, IL-10R2 is also part of the receptor complexes for other ligands in the IL-10 family of cytokines. The affinity for IL-10 is higher for the IL-10R complex than for IL-10R1 alone.<ref~~>Sabat, Robert. IL-10 family of cytokines. Cytokine Growth Factor Rev. 2010; 21:315–324<~~/ref> IL-10 is a pleiotropic cytokine in that it has an effect on many different immune cells, including T-cells, B-cells, macrophages and mast cells.<ref>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; 174(5):1209-1220</ref> When IL-10 binds the extracellular domain of the IL-10R1 receptor, two tyrosine-kinases, JAK1 and Tyk2 become phosphorylated, which in turn phosphorylate the internal domain of IL-10R1. This then binds the transcription factor STAT3, which becomes phosphorylated, dimerizes, and moves into the nucleus. In the nucleus, STAT3 binds to the promoters of various genes, resulting in decreased expression of inflammatory cytokines such as IFNγ, TNFα, and GM-CSF.<ref>Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/></ref> IL-10R2 acts as an accessory subunit for signaling, rather than for ligand binding. It recruits the Tyk2 tyrosine kinase into the signaling complex described above.<scene name='56/564053/Il_10-il_10r1/3'>IL-10 bound to IL-10R1</scene> forms a tetramer, made up of the dimeric two-domain IL-10 molecule and two IL-10R1 receptors.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref>The IL-10R1 receptor in this image is shown in dark blue.

Most hematopoietic cells express the IL-10 transmembrane receptors, IL-10R1 and IL-10R2. While IL-10R1 is specific only for IL-10 cytokine, IL-10R2 is also part of the receptor complexes for other ligands in the IL-10 family of cytokines. The affinity for IL-10 is higher for the IL-10R complex than for IL-10R1 alone.<ref name="sabat" /ref> IL-10 is a pleiotropic cytokine in that it has an effect on many different immune cells, including T-cells, B-cells, macrophages and mast cells.<ref>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; 174(5):1209-1220</ref> When IL-10 binds the extracellular domain of the IL-10R1 receptor, two tyrosine-kinases, JAK1 and Tyk2 become phosphorylated, which in turn phosphorylate the internal domain of IL-10R1. This then binds the transcription factor STAT3, which becomes phosphorylated, dimerizes, and moves into the nucleus. In the nucleus, STAT3 binds to the promoters of various genes, resulting in decreased expression of inflammatory cytokines such as IFNγ, TNFα, and GM-CSF.<ref>Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/></ref> IL-10R2 acts as an accessory subunit for signaling, rather than for ligand binding. It recruits the Tyk2 tyrosine kinase into the signaling complex described above.<scene name='56/564053/Il_10-il_10r1/3'>IL-10 bound to IL-10R1</scene> forms a tetramer, made up of the dimeric two-domain IL-10 molecule and two IL-10R1 receptors.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref>The IL-10R1 receptor in this image is shown in dark blue.

== Implications or Possible Application ==

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 == Introduction ==
 <Structure load='2H24' size='300' frame='true' align='right' caption='The interleukin 10 monomer. PDB 2H24' scene='Insert optional scene name here' />
-Interleukin 10 (IL-10) belongs to a class of proteins called cytokines. Cytokines are chemical messengers that are produced by and act on cells of the immune system.<ref>National Institute of Allergy and Infectious Diseases, ”Immune Cells and their Products: Cytokines”. Web. 16Nov2013 <http://www.niaid.nih.gov/topics/immuneSystem/immuneCells/Pages/cytokines.aspx></ref>   It is also part of the IL-10 family of cytokines, which also includes IL-19, IL-20, IL-22, IL-24 and IL-26.  This grouping was made based on similarities in structure, function, and location of the encoding genes.<ref>Sabat, Robert. IL-10 family of cytokines.  Cytokine Growth Factor Rev. 2010; 21:315–324</ref>  IL-10 has also previously been called cytokine synthesis inhibitory factor (CSIF) because of its anti-inflammatory properties and ability to inhibit the production of other cytokines.<ref>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; 174(5):1209-1220</ref>  The ability to limit the immune response to pathogens is crucial to preventing self-inflicted damage to the host. This cytokine is expressed in many eukaryotic hosts, as well as some viruses. A quick protein BLAST of the human IL-10 sequence reveals homology with IL-10 of many other primate species, as well as that found in bats, horses, elephants, rodents, sheep, cats and birds.  The remainder of this page will focus on human IL-10.
+Interleukin 10 (IL-10) belongs to a class of proteins called cytokines. Cytokines are chemical messengers that are produced by and act on cells of the immune system.<ref>National Institute of Allergy and Infectious Diseases, ”Immune Cells and their Products: Cytokines”. Web. 16Nov2013 <http://www.niaid.nih.gov/topics/immuneSystem/immuneCells/Pages/cytokines.aspx></ref>   It is also part of the IL-10 family of cytokines, which also includes IL-19, IL-20, IL-22, IL-24 and IL-26.  This grouping was made based on similarities in structure, function, and location of the encoding genes.<ref name="sabat">Sabat, Robert. IL-10 family of cytokines.  Cytokine Growth Factor Rev. 2010; 21:315–324</ref>  IL-10 has also previously been called cytokine synthesis inhibitory factor (CSIF) because of its anti-inflammatory properties and ability to inhibit the production of other cytokines.<ref>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; 174(5):1209-1220</ref>  The ability to limit the immune response to pathogens is crucial to preventing self-inflicted damage to the host. This cytokine is expressed in many eukaryotic hosts, as well as some viruses. A quick protein BLAST of the human IL-10 sequence reveals homology with IL-10 of many other primate species, as well as that found in bats, horses, elephants, rodents, sheep, cats and birds.  The remainder of this page will focus on human IL-10.
 == Structure ==
@@ Line 16: / Line 16: @@
 == Mechanism of Action ==
-Most hematopoietic cells express the IL-10 transmembrane receptors, IL-10R1 and IL-10R2.  While IL-10R1 is specific only for IL-10 cytokine, IL-10R2 is also part of the receptor complexes for other ligands in the IL-10 family of cytokines.  The affinity for IL-10 is higher for the IL-10R complex than for IL-10R1 alone.<ref>Sabat, Robert. IL-10 family of cytokines.  Cytokine Growth Factor Rev. 2010; 21:315–324</ref> IL-10 is a pleiotropic cytokine in that it has an effect on many different immune cells, including T-cells, B-cells, macrophages and mast cells.<ref>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; 174(5):1209-1220</ref> When IL-10 binds the extracellular domain of the IL-10R1 receptor, two tyrosine-kinases, JAK1 and Tyk2 become phosphorylated, which in turn phosphorylate the internal domain of IL-10R1. This then binds the transcription factor STAT3, which becomes phosphorylated, dimerizes, and moves into the nucleus.  In the nucleus, STAT3 binds to the promoters of various genes, resulting in decreased expression of inflammatory cytokines  such as IFNγ, TNFα, and GM-CSF.<ref>Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/></ref> IL-10R2 acts as an accessory subunit for signaling, rather than for ligand binding. It recruits the Tyk2 tyrosine kinase into the signaling complex described above.<scene name='56/564053/Il_10-il_10r1/3'>IL-10 bound to IL-10R1</scene> forms a tetramer, made up of the dimeric two-domain IL-10 molecule and two IL-10R1 receptors.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref>The IL-10R1 receptor in this image is shown in dark blue.
+Most hematopoietic cells express the IL-10 transmembrane receptors, IL-10R1 and IL-10R2.  While IL-10R1 is specific only for IL-10 cytokine, IL-10R2 is also part of the receptor complexes for other ligands in the IL-10 family of cytokines.  The affinity for IL-10 is higher for the IL-10R complex than for IL-10R1 alone.<ref name="sabat" /ref> IL-10 is a pleiotropic cytokine in that it has an effect on many different immune cells, including T-cells, B-cells, macrophages and mast cells.<ref>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; 174(5):1209-1220</ref> When IL-10 binds the extracellular domain of the IL-10R1 receptor, two tyrosine-kinases, JAK1 and Tyk2 become phosphorylated, which in turn phosphorylate the internal domain of IL-10R1. This then binds the transcription factor STAT3, which becomes phosphorylated, dimerizes, and moves into the nucleus.  In the nucleus, STAT3 binds to the promoters of various genes, resulting in decreased expression of inflammatory cytokines  such as IFNγ, TNFα, and GM-CSF.<ref>Thompson Reuters. Web. 16Nov2013. <http://pathwaymaps.com/maps/531/></ref> IL-10R2 acts as an accessory subunit for signaling, rather than for ligand binding. It recruits the Tyk2 tyrosine kinase into the signaling complex described above.<scene name='56/564053/Il_10-il_10r1/3'>IL-10 bound to IL-10R1</scene> forms a tetramer, made up of the dimeric two-domain IL-10 molecule and two IL-10R1 receptors.<ref>Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the Interleukin-10 receptor. Annu. Rev. Immunol. 2001.19:683-765</ref>The IL-10R1 receptor in this image is shown in dark blue.
 == Implications or Possible Application ==