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UdA CYTOKINES AND CHEMOKINE IN INFLAMMATION: Dr. P. Conti - PowerPoint PPT Presentation

Professor Pio Conti Director of the Division of Immunology University of Chieti ITALY UdA CYTOKINES AND CHEMOKINE IN INFLAMMATION: Dr. P. Conti Cytokine are proteis secreted by the cells of innate and adaptive immunity that


  1. Professor Pio Conti Director of the Division of Immunology University of Chieti ITALY Ud’A

  2. CYTOKINES AND CHEMOKINE IN INFLAMMATION: Dr. P. Conti • Cytokine are proteis secreted by the cells of innate and adaptive immunity that mediate many of the functions of these cells. • Cytokines are produced in response to microbes and other antigens. • Different cytokine stimulate diverse responses of cells involved in immunity and inflammation. • Nomenclature:monokines, lymphokines, cytokines, interleukines, chemokines. • Cytokines are pleiotropic and redundantand and they also have an autocrine action.

  3. T and B LYMPHOCYTES

  4. T-cell activation Macrofago presentante l’antigene (APC) MHC CD4 o Antigene CD8 TCR CD3 Ud’A Linfocita T Producing Cytokines & Chemokines Professor P. Conti Division of Immunology University of Chieti - ITALY

  5. B and T-cell activation by the antigen Ag macrofago Fagocitosi dell’Ag Macrofago attivato Antigene processato Linfocita B Linfocita B IL-1 Presentazione dell’Ag al linfocita B Recettore per l’Ag MHC Ag Clone cellulare IL-1 Linfocita B attivato TCR/CD3 macrofago Linfocita T Ud’A Clone cellulare Linfocita T attivato Professor P. Conti Division of Immunology University of Chieti - ITALY

  6. Cytokines and inflammatory cells starting from stem cells Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  7. Hypersensitivity Type IV Activated lymphocyte produce cytokines:actvation of macrophage and release of inflammatory monokines. Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  8. Comparison of the biologic properties of monokines: IL-1, TNF and IL-6 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  9. BIOLOGICAL EFFECTS OF IL-1 Aspects of the acute phase response mediated by IL-1 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  10. IL-1 downregulation by IL-4, IL-6, PGE and IL-1ra (network) Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  11. IL-6 and B lymphocyte activation IL-6 binds B cell IL-6Ra Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  12. IL-6 production and its involvement in disease Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  13. Maturation of mast cells and IL-6 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  14. IL-32 Manuscript n preparation 2007-2008 IL-32 α A PRO-INFLAMMATORY CYTOKINE IN RAT PAW INJECTION SITE ACTIVATES COX-2 GENE EXPRESSION AND STIMULATES PGE 2 GENERATION : LACK OF EFFECT ON PGD 2 , HDC mRNA EXPRESSION, HISTAMINE AND TRYPTASE RELEASE IN CORD BLOOD MAST CELLS 1 Castellani M.L., 2 Kempura D.J, 2 Boucher W., 2 Tagen M., 3 Frydas S., 4 Perrella A., 2 Theoharides T.C., 5 Neri G., 6 Cerulli G. and 1 Conti P. 1 Immunology Division, Medical School, University of Chieti-Pescara, Italy; 2 Department of Pharmacology and Experimental Therapeutics, Biochemistry and Internal Medicine Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA, USA ; 3 Laboratory of Parasitology, Veterinary Faculty, Aristotele University, Thessaloniki, Greece. 4 Infectious Diseases, University of Napoli, Italy. 5 ENT Division, University of Chieti-Pescara, and 6 Orthopaedic Division, University of Perugia, Italy Interleukin-32 (IL-32) is one of the latest described inflammatory cytokine, closely related to IL-1, although, the structure and the receptors are clearly distinct. IL-32 is produced by T cells, NK cells, epithelial cells and monocytes/macrophages and its transcripts are highly expressed in immune tissues. IL-32 is a pro-inflammatory cytokine capable to induce other pro-inflammatory cytokines, such as IL-1, IL-6, TNF-alpha and IL-8 (CXCL8). Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  15. IL-32 inflammatory effect on the rat paw PBS IL-32 Ud’A Anti-IL-32 Anti-IL-32 + IL-32 Professor P. Conti Division of Immunology University of Chieti - ITALY

  16. IL-32 failed to stimulate tryptase release in human mast cells Tryptase production from human cord blood-derived mast cells Tryptase (mg/ml) Three experiments in triplicate Groups 1 2 3 Control 2.3 ± 0.5 2.0 ± 0.6 2.1 ± 0.7 10 μ g/ml Anti-IgE 510 ± 80 480 ± 110 390 ± 90 IL-32 α 20 μ g/ml 1.8 ± 0.3 2.4 ± 0.9 1.9 ± 0.6 IL-32 α 50 μ g/ml 1.7 ± 0.5 2.1 ± 0.6 2.2 ± 0.8 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  17. The biology of IL-33: the latest interleukin - IL-33 is the natural ligand of the IL-1 receptor family member ST2L - IL-33 is involved in allergic inflammatory responses through the production of cytokines released by Th2 cells. -IL-33 stimulates mast cell to produce pro-inflammatory cytokines and mediates allergic disorders. -IL-33 accelerates the maturation of CD34+ mast cell precursor of human cord blood-derived mast cells. -IL-33 induces the production of Th2 cytokines and is produced in the sera of asthmatic patients. - IL-33 is a selective Th2 chemoattractant. -IL-33 mediates IL-8 production by human cord blood mast cells. Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  18. Expression and secretion of rantes (CCL5) in granulomatous calcified tissue before and after lipopolysaccharide treatment In vivo We induced an experimental chronic inflammatory state in rats by subcutaneous injection (0.2 ml) of a saturated water solution (1:40) potassium permanganate (KMnO 4 ) . This treatment causes the formation of calcified granulomatous tissue at the site of injection, reaching the apex in size and weight after one week. Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  19. RANTES IN GRANULOMA RANTES concentration (pg/ml/100 mg), determined by ELISA, in the conditioned medium from minced granuloma tissue induced in rats with KMnO 4 and i.p.-treated in vivo with LPS or Dex or PBS. LPS (100 ng/ml) or nothing was added in vitro in all specimens from previously i.p.-treated animals. RANTES pg/ml/100 mg tissue Treatment No. of -LPS +LPS P<0. Δ % in vivo animals in vitro in vitro 05 1430 ± PBS (0.05 + 214.28 12 455 ± 82 (control) 275 ) % 3560 ± (0.01 LPS 12 1680 ± 395 +111.9 % 195 ) (N.S. + 69.1 % Dex 12 337 ± 20 570 ± 150 ) % Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  20. IL-10 network Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  21. IL-10 immunostimulatory effects Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  22. IL-10 and mast cells Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  23. Chemokines (I) Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  24. Chemokines (II) Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  25. Chemokines (III) Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  26. Dermal response to exogenous human RANTES Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  27. Mast cell migration induced by RANTES Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  28. RANTES and HDC Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  29. IL-19, IL-20, IL-22, IL-24, and IL-26 network and biological effects Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  30. IL-19 network Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  31. IL-21 network Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  32. IL-22 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  33. IL-25 Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  34. HIV infection of CD4 + lymphocytes Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  35. Tumor and cytokines Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  36. Tumor and cytokines Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  37. Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  38. Differential production of IL-1 and IL-1 receptor antagonist (IL-1Ra) Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  39. IL-15 binds the IL-12 receptor Ud’A Professor P. Conti Division of Immunology University of Chieti - ITALY

  40. IL-15 IS STRUCTURAL HOMOLOGUS TO IL-2 • IL-15 IS A CYTOKINE PRODUCED BY MONONUCLEAR CELLS IN RESPONSE TO VIRAL INFECTION, LPS AND OTHER SIGNALS. • IL-15 ACTS A T-CELL GROWTH FACTOR ON LONG LIVED MEMORY CD8+ T CELLS. • IL-15 KNOCKOUT MICE HAVE GREATLY REDUCED NUMBERS OF NK AND CD8+ CELLS.

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