citoquinas 2005 3 - alergomurcia · 2020-04-17 · de cel t actv. y cel. nk induce th-o a th-1...
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Las Citocinas (III)Las Citocinas (III)
Dr. Juan Rodríguez-Tafur D.Profesor Asociado de Farmacología e Inmunología
Laboratorio de Farmacología de la Respuesta InmuneCoordinador del Comité de Residentado Médico de
Inmunología Clinica y AlergologíaFacultad de Medicina – UNMSM
Lima (Perú)
Dr. Juan Rodríguez-Tafur D.Profesor Asociado de Farmacología e Inmunología
Laboratorio de Farmacología de la Respuesta InmuneCoordinador del Comité de Residentado Médico de
Inmunología Clinica y AlergologíaFacultad de Medicina – UNMSM
Lima (Perú)
Agosto 2005
OTRAS CITOQUINASOTRAS CITOQUINAS
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INTERLEUQUINA-7 (IL-7)
GLICOPROTEINA DE 25 KD
ES PRODUCIDA EN EL TIMO, EL BAZO Y CELULAS ESTROMAL DE LA M.O.
MEJORA LA ADHESION DE β INTEGRINAS DEL TIMOCITO A LA MATRIX PROTEICA
MITOGENO (CON SCF) DE TIMOCITOS Y CEL PRE-B
MEJORA LA FUNCION DE CEL. CITOTOXICAS
DEFICIT EN ANIMALES PRODUCE HIPOPLASIA LINFOIDE DE CELULAS T Y B.
INTERLEUQUINA-7 (IL-7)
GLICOPROTEINA DE 25 KD
ES PRODUCIDA EN EL TIMO, EL BAZO Y CELULAS ESTROMAL DE LA M.O.
MEJORA LA ADHESION DE β INTEGRINAS DEL TIMOCITO A LA MATRIX PROTEICA
MITOGENO (CON SCF) DE TIMOCITOS Y CEL PRE-B
MEJORA LA FUNCION DE CEL. CITOTOXICAS
DEFICIT EN ANIMALES PRODUCE HIPOPLASIA LINFOIDE DE CELULAS T Y B.
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PROTEINA DE 19 KD
ACTUA COMO FACTOR DE CRECIMIENTO DE CELULAS BLASTICAS
SINERGISMO CON IL-3, IL-4, CSF-GM
ROL IMPORTANTE EL HEMATOPOIESIS, LINFOPOIESIS, DESARROLLO DE ADIPOCITOS,NEURONAS Y OSTEOCLASTOS
CON IL-3 INCREMENTAN EL NUMERO Y TAMAÑO DE LAS COLONIAS DE MEGACARIOCITOS
PROTEINA DE 19 KD
ACTUA COMO FACTOR DE CRECIMIENTO DE CELULAS BLASTICAS
SINERGISMO CON IL-3, IL-4, CSF-GM
ROL IMPORTANTE EL HEMATOPOIESIS, LINFOPOIESIS, DESARROLLO DE ADIPOCITOS,NEURONAS Y OSTEOCLASTOS
CON IL-3 INCREMENTAN EL NUMERO Y TAMAÑO DE LAS COLONIAS DE MEGACARIOCITOS
Nordan RP, Potter M Science 233(4763):566-9 (1986)Paul SR y col. Proc. Natl. Acad. Sci. USA 87:7512 (1990)Nordan RP, Potter M Science 233(4763):566-9 (1986)Paul SR y col. Proc. Natl. Acad. Sci. USA 87:7512 (1990)
HETERODIMERO DE 2 SUBUNIDADES DE 35 Y 40 KD
LA PRODUCC. DE IL-12 ES ACTV. POR MACROFAGOSY ES INHIBIDO POR IL-4 Y POR IL-10
INDUCE PRODUCCION DE IFN-γ, PROMUEVE LA PROLIF. DE CEL T ACTV. Y CEL. NKINDUCE TH-O A TH-1 SUPRIME TH-2 INDUCE PRODUCION DE CSF-GM, TNF, IL-6 , EN MENOR PROPORCION IL-2 (ACCION SINERGICA CON IL-2)
HETERODIMERO DE 2 SUBUNIDADES DE 35 Y 40 KD
LA PRODUCC. DE IL-12 ES ACTV. POR MACROFAGOSY ES INHIBIDO POR IL-4 Y POR IL-10
INDUCE PRODUCCION DE IFN-γ, PROMUEVE LA PROLIF. DE CEL T ACTV. Y CEL. NKINDUCE TH-O A TH-1 SUPRIME TH-2 INDUCE PRODUCION DE CSF-GM, TNF, IL-6 , EN MENOR PROPORCION IL-2 (ACCION SINERGICA CON IL-2)
Gately y col. J. Immunol. 136,1274-1281 (1986)Wong y col. Cell Immunol. 111,39-54 (1987)
Gately y col. J. Immunol. 136,1274-1281 (1986)Wong y col. Cell Immunol. 111,39-54 (1987)
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GLICOPROTEINA DE 50-60 KD ANTES CONOCIDO COMO FACT. DE CRECIMIENTO DE CELULAS B DE ALTO PESO MOLECULAR ES PRODUCIDA POR CEL. DENDRITICAS FOLICULARES Y CELULAS T ES MITOGENO DE CELULAS B ACTIVADAS
GLICOPROTEINA DE 50-60 KD ANTES CONOCIDO COMO FACT. DE CRECIMIENTO DE CELULAS B DE ALTO PESO MOLECULAR ES PRODUCIDA POR CEL. DENDRITICAS FOLICULARES Y CELULAS T ES MITOGENO DE CELULAS B ACTIVADAS
Pre - BPre - B
BBmemoriamemoria
TT IL-14IL-14
Ambrus,J.L. and Fauci,A.S. J. Clin. Invest. 75,732-739 (1985)Ambrus,J.L. and Fauci,A.S. J. Clin. Invest. 75,732-739 (1985)
Céls dendríticasfolicularesCéls dendríticasfoliculares
INTERLEUQUINA-15 (IL-15)
PRODUCIDO POR CEL. EPITELIALES Y MONOCITOSPERO NO POR LINFOCITOS T
INDUCE PROLIF DE CEL T ACTIVAS
GENERA CEL T CITOTOXICAS ESPECIFICAS
SE EXPRESA EN PLACENTA, MUSC. ESQUEL, RINON, PULMON, HIGADO, CORAZON Y ESTROMA DE M.O.
IL-2, IL-4, IL-7, IL-9, IL-15 COMPATEN EL RECEPTOR(IL-2Rγ, SU DEFICIENCIA PRODUCE X-SCID)
INTERLEUQUINA-15 (IL-15)
PRODUCIDO POR CEL. EPITELIALES Y MONOCITOSPERO NO POR LINFOCITOS T
INDUCE PROLIF DE CEL T ACTIVAS
GENERA CEL T CITOTOXICAS ESPECIFICAS
SE EXPRESA EN PLACENTA, MUSC. ESQUEL, RINON, PULMON, HIGADO, CORAZON Y ESTROMA DE M.O.
IL-2, IL-4, IL-7, IL-9, IL-15 COMPATEN EL RECEPTOR(IL-2Rγ, SU DEFICIENCIA PRODUCE X-SCID)
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CD8+CD8+ IL-16IL-16
CD4+CD4+
SUPRIMEINFECCIONSUPRIMESUPRIMEINFECCIONINFECCION
HIVHIVHIV
Kurth, R. Nature Dec 1995.KurthKurth, R. , R. NatureNature DecDec 1995.1995.
CONOCIDO ANTES COMO LCF (FACTOR QUIMIO-ATRAYENTE DE LINFOCITOS)
INDUCE LA MIGRACION DIRECCIONAL DE CD4+, EOSINOFILOS Y MONOCITOS
↑ IL-2Rα ↑ CMH-II EN CELULAS T
CONOCIDO ANTES COMO LCF (FACTOR QUIMIO-ATRAYENTE DE LINFOCITOS)
INDUCE LA MIGRACION DIRECCIONAL DE CD4+, EOSINOFILOS Y MONOCITOS
↑ IL-2Rα ↑ CMH-II EN CELULAS T
IL-17 (cytotoxic T-lymphocyte-associated antigen-8 CTLA-8)
Estímulo
Célula T
Fibroblasto
PRODUCIDA POR CELULAS T
ACTIVA AL FACTOR DE TRANSDUCCION NF-κBINDUCE LA EXPRESION DE VARIAS CITOQUINASPROINFLAMATORIAS Y DE ICAM-1
ACTUA SOBRE RECEPTORES DE UNA GRAN VARIEDAD DE CELULAS
PRODUCIDA POR CELULAS T
ACTIVA AL FACTOR DE TRANSDUCCION NF-κBINDUCE LA EXPRESION DE VARIAS CITOQUINASPROINFLAMATORIAS Y DE ICAM-1
ACTUA SOBRE RECEPTORES DE UNA GRAN VARIEDAD DE CELULAS
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Apoptosis de Célulasque expresan FAS
Antígeno
Antígeno
Activación deMacrófagos
INTERLEUQUINA-18 (IL-18)
PROTEINA DE 17 KD
PRODUCIDA POR CEL T ACTIVAS, ACTIVA CEL T Y ACTUA SOBRE MUCHAS OTRAS CEL COMO PRO-INFLAMATORIA
TAMBIEN DENOMINADA FACTOR INDUCTOR DE IFN-γ.
ESTRUCTURA SIMILAR A IL-1α, IL-1β E IL-1RA SE PROPOSO DENOMINARLA IL-1γ
INDUCE IFN- γ E INHIBE IL-10. FUNCION SIMILAR Y SINERGICA CON IL-12
INTERLEUQUINA-18 (IL-18)
PROTEINA DE 17 KD
PRODUCIDA POR CEL T ACTIVAS, ACTIVA CEL T Y ACTUA SOBRE MUCHAS OTRAS CEL COMO PRO-INFLAMATORIA
TAMBIEN DENOMINADA FACTOR INDUCTOR DE IFN-γ.
ESTRUCTURA SIMILAR A IL-1α, IL-1β E IL-1RA SE PROPOSO DENOMINARLA IL-1γ
INDUCE IFN- γ E INHIBE IL-10. FUNCION SIMILAR Y SINERGICA CON IL-12
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Cell 2001 Jan 12;104(1):9-19
Interleukin 20: discovery, receptor identification, and role in epidermal function.
Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek L, Kelly JD, Madden K, Maurer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA
Department of Genetics, ZymoGenetics, Inc., 1201 Eastlake Avenue E, Seattle, WA 98102, USA.
A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.
Cell 2001 Jan 12;104(1):9-19
Interleukin 20: discovery, receptor identification, and role in epidermal function.
Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, Eagan M, Foster D, Haldeman BA, Hammond A, Haugen H, Jelinek L, Kelly JD, Madden K, Maurer MF, Parrish-Novak J, Prunkard D, Sexson S, Sprecher C, Waggie K, West J, Whitmore TE, Yao L, Kuechle MK, Dale BA, Chandrasekher YA
Department of Genetics, ZymoGenetics, Inc., 1201 Eastlake Avenue E, Seattle, WA 98102, USA.
A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.
Immunol 2001 Oct 1;167(7):3545-9
Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types.
Dumoutier L, Leemans C, Lejeune D, Kotenko SV, Renauld JC
IL-10-related cytokines include IL-20 and IL-22, which induce, respectively, keratinocyte proliferation and acute phase production by hepatocytes, as well as IL-19, melanoma differentiation-associated gene 7, and AK155, three cytokines for which no activity nor receptorcomplex has been described thus far. Taken together, these results demonstrate that: 1) IL-20 induces STAT activation through IL-20R complexes of two types; 2) mda-7 and IL-20 redundantly signal through both complexes; and 3) IL-19 signals only through the type I IL-20R complex.
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Immunity 2000 Nov;13(5):715-25
Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA
DNAX Research Institute, Palo Alto, CA 94304, USA.
A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.
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J Biol Chem 2001 Nov 12;
Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2.
Wang M, Tan Z, Zhang R, Kotenko SV, Liang P
Interleukin 24 (IL-24) encodes a secreted protein that exhibits significant homology to the interleukin 10 (IL-10) family of cytokines. Here we show that the human IL-24 is secreted by activated peripheral blood mononuclear cells (PBMCs) and is the ligand for two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. The latter is also the receptor for IL-20. Cos cells transfected with either IL-24 receptor heterodimers bind the ligand with similar saturation kinetics. IL-24 binding to either its endogenous receptors on human keratinocytes or to ectopically expressed receptors on baby hamster kidney (BHK) cells leads to activation of the signal transducers and activators of transcription (STATs). Taken together, these results provide compelling evidence for IL-24 being the fourth member of IL-10 family of cytokines to which their specific receptors have been identified.
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Eta-1/OpEta-1/OpMO
CD51-61( αV-ß3)CD51-61( αV-ß3)
RGDRGD
• Reclutamiento celular• Disminuye Sintasa de ON• Regula remodelación tisular
“EL SWITH TH1- TH2 ES UN PASO CRITICO QUE
DETERMINA LA PROGRESION CLINICA DE UNA ENFERMEDAD”
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Balance Inmune
TH-1 TH-2
TH-2
TH-1
IL-12
Disbalance Inmune Th1
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Disbalance Inmune Th2
TH-2
TH-1IL-4 IL-10
TH-1
TH-2
Treg
Regulación Th1/Th2 x Treg