Citochine Sono fattori proteici, secreti dai linfociti e dai monociti, capaci di influenzare tutte le fasi del processo infiamm. e pertanto di regolano l'ampiezza e la durata della risposta infiammatoria (e immunitaria) I loro effetti sono: - pleiotropici, perchè possono agire su diversi tipi di cellule - ridondanti e possono influenzare la sintesi di altre citochine - multifunzionali in quanto una singola citochina può avere effetti sia positivi che negativi La loro sintesi e' un fenomeno di breve durata e rigidamente controllato: gli stimoli infiammtori, per meccanismi recettoriali, attivano il fattore di trascrizione NF-KB Possonono avere un effetto autocrino, paracrino, endocrino
Contactin-like (C) domain Cytokine receptor superfamily (CR) domain OLD - fibronectin type III-like c. 90 residues, with 4 or 6 disulphide bond Fibronectin type III domain (F3) Immunoglobulin superfamily domain (Ig) Nerve growth factor (NGF) / Tumor necrosis factor (TNF) receptor superfamily domain c. 90 residues, with no disulphides c. 100 residues with 0 to 6 disulphide bonds c. 40 residues with 6 or 8 disulphide bonds Domain (module) types present in cytokine receptors
Receptor composition (extra-cellular portions) IL-2R (beta and gamma), IL-4R (alpha and gamma),IL-7R (alpha and gamma), GHR (B and C), EPOR (B and C) IL-3R (alpha),IL-5R (alpha), IL-6R (alpha + ), CNTFR (alpha), IL-12R, GM-CSFR(alpha) IL-6R, LIFR, OSMR, CNTFR, G-CSFR, IL-12R LIFR (alpha), CNTFR IL-3R (beta), IL-5R (beta), GM-CSF (beta) TNFR p55
CytokinePossible Clinical Use Treatment or Diagnosis Bone Morphogenetic ProteinsFracture treatment Interleukin-1 Receptor AntagonistAnti-inflammation in rheumatoid arthritis Interleukin-10 (IL-10)Cancer lymphoma *multiple myeloma *melanoma *ovarian Anti-inflammation Transplantation Immunodeficiencies Parasitic Infections Interleukin-11 (IL-11)Breast Cancer Interleukin-12 (IL-12)Cancer HIV Interleukin-13 (IL-13)Anti-inflammation Interleukin-14 (IL-14)Various lymphomas Monocyte Chemoattractant Protein-1Atherosclerosis Pulmonary fibrosis
Beta Beta-Trefoil Interleukin 1-alpha (IL1-A), Interleukin 1-beta (IL1-B), Fibroblast growth factor (FGF) Beta-sandwich Tumour Necrosis Factor alpha (TNF-A), Tumour Necrosis Factor beta (TNF-B) EGF-like Transforming growth factor alpha (TGF-A) Cystine knot dimerization domains Gonadotropin, Nerve Growth Factor (NGF), Platelet-derived growth factor (PDGF), Transforming growth factor beta2 (TGF-B2) Alpha + Beta IL-8, IP10, platelet factor 4 (PF-4), bTG, GRO, 9E3, HLA-A2, macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta), Melanoma growth stimulating activity (MGSA)