Apilimod inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis

PLoS ONE

Volumn 7, Issue 4, 2012, Pages

  Wada, Yumiko ^a   Cardinale, Irma ^b   Khatcherian, Artemis ^b   Chu, John ^a   Kantor, Aaron B ^c   Gottlieb, Alice B ^d   Tatsuta, Noriaki ^a   Jacobson, Eric ^a   Barsoum, James ^a   Krueger, James G ^b  

^a Synta Pharmaceuticals Corp   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

^c Pharmaceutical Product Development   (United States)

^d TUFTS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APILIMOD; CD11 ANTIGEN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 23; PROTEIN P19; PROTEIN P40; LEUKOCYTE ANTIGEN; MORPHOLINE DERIVATIVE; TRIAZINE DERIVATIVE;

ADULT; AGED; ARTICLE; CELL INFILTRATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG MECHANISM; FEMALE; GENE; GENE EXPRESSION REGULATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; IN VITRO STUDY; INTERLEUKIN 12 GENE; INTERLEUKIN 23 GENE; MALE; MOLECULAR PATHOLOGY; OUTCOME ASSESSMENT; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PSORIASIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SKIN DEFECT; TH1 CELL; TH17 CELL; ADOLESCENT; B LYMPHOCYTE; BIOSYNTHESIS; CELL MOTION; CLINICAL TRIAL; DRUG ANTAGONISM; DRUG EFFECT; EOSINOPHIL; IMMUNOLOGY; MIDDLE AGED; MULTICENTER STUDY; NEUTROPHIL; ORAL DRUG ADMINISTRATION; PATHOLOGY; SKIN;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; ANTIGENS, CD; B-LYMPHOCYTES; CELL MOVEMENT; DENDRITIC CELLS; EOSINOPHILS; FEMALE; HUMANS; INTERLEUKIN-12; INTERLEUKIN-23; MALE; MIDDLE AGED; MORPHOLINES; NEUTROPHILS; PSORIASIS; SKIN; TH1 CELLS; TH17 CELLS; TRIAZINES;

EID: 84859499638     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0035069     Document Type: Article

References (43)

1. Lebwohl M, (2003) Psoriasis. Lancet 361: 1197-1204.
2. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, et al. (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445: 648-651.
3. Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, et al. (2006) IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 203: 2577-2587.
4. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, et al. (2004) Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199: 125-130.
5. Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, et al. (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128: 1207-1211.
6. Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, et al. (2008) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181: 4733-4741.
7. Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, et al. (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80: 273-290.
8. Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, et al. (2005) Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A 102: 2075-2080.
9. Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, et al. (2005) TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol 175: 2721-2729.
10. Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, et al. (2007) A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 356: 580-592.
11. Strober BE, Crowley JJ, Yamauchi PS, Olds M, Williams DA, (2011) Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 165: 661-668.
12. Gottlieb AB, Leonardi C, Kerdel F, Mehlis S, Olds M, et al. (2011) Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 165: 652-660.
13. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, et al. (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371: 1665-1674.
14. Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, et al. (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371: 1675-1684.
15. Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin SL, et al. (2005) Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci U S A 102: 19057-19062.
16. Wang H, Peters T, Kess D, Sindrilaru A, Oreshkova T, et al. (2006) Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. J Clin Invest 116: 2105-2114.
17. Lowes MA, Bowcock AM, Krueger JG, (2007) Pathogenesis and therapy of psoriasis. Nature 445: 866-873.
18. Wada Y, Lu R, Zhou D, Chu J, Przewloka T, et al. (2007) Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood 109: 1156-1164.
19. Laborda J, (1991) 36B4 cDNA used as an estradiol-independent mRNA control is the cDNA for human acidic ribosomal phosphoprotein PO. Nucleic Acids Res 19: 3998.
20. Lew W, Bowcock AM, Krueger JG, (2004) Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and "Type 1" inflammatory gene expression. Trends Immunol 25: 295-305.
21. Schon MP, Ludwig RJ, (2005) Lymphocyte trafficking to inflamed skin-molecular mechanisms and implications for therapeutic target molecules. Expert Opin Ther Targets 9: 225-243.
22. Boiardi L, Salvarani C, Macchioni P, Casadei Maldini M, Mancini R, et al. (1992) Immunologic effects in patients with psoriatic arthritis treated with cyclosporine A. J Rheumatol 19: 1933-1937.
23. Carmody RJ, Ruan Q, Liou HC, Chen YH, (2007) Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells. J Immunol 178: 186-191.
24. Grumont R, Hochrein H, O'Keeffe M, Gugasyan R, White C, et al. (2001) c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription. J Exp Med 194 1021-1032.
25. Mason N, Aliberti J, Caamano JC, Liou HC, Hunter CA, (2002) Cutting edge: identification of c-Rel-dependent and-independent pathways of IL-12 production during infectious and inflammatory stimuli. J Immunol 168: 2590-2594.
26. Sanjabi S, Hoffmann A, Liou HC, Baltimore D, Smale ST, (2000) Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Proc Natl Acad Sci U S A 97: 12705-12710.
27. Trepicchio WL, Ozawa M, Walters IB, Kikuchi T, Gilleaudeau P, et al. (1999) Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions. J Clin Invest 104: 1527-1537.
28. Yawalkar N, Karlen S, Hunger R, Brand CU, Braathen LR, (1998) Expression of interleukin-12 is increased in psoriatic skin. J Invest Dermatol 111: 1053-1057.
29. Toichi E, Torres G, McCormick TS, Chang T, Mascelli MA, et al. (2006) An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J Immunol 177: 4917-4926.
30. Asadullah K, Sterry W, Volk HD, (2003) Interleukin-10 therapy--review of a new approach. Pharmacol Rev 55: 241-269.
31. Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ, (2005) Sargramostim for active Crohn's disease. N Engl J Med 352: 2193-2201.
32. Asadullah K, Docke WD, Ebeling M, Friedrich M, Belbe G, et al. (1999) Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Arch Dermatol 135: 187-192.
33. Asadullah K, Friedrich M, Hanneken S, Rohrbach C, Audring H, et al. (2001) Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histologic, immunohistologic, and molecular biology findings. J Invest Dermatol 116: 721-727.
34. Friedrich M, Docke WD, Klein A, Philipp S, Volk HD, et al. (2002) Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in Psoriasis. J Invest Dermatol 118: 672-677.
35. Hilliard BA, Mason N, Xu L, Sun J, Lamhamedi-Cherradi SE, et al. (2002) Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation. J Clin Invest 110: 843-850.
36. Grigoriadis G, Zhan Y, Grumont RJ, Metcalf D, Handman E, et al. (1996) The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations. Embo J 15: 7099-7107.
37. Park AY, Hondowicz B, Kopf M, Scott P, (2002) The role of IL-12 in maintaining resistance to Leishmania major. J Immunol 168: 5771-5777.
38. Benson JM, Sachs CW, Treacy G, Zhou H, Pendley CE, et al. (2011) Therapeutic targeting of the IL-12/23 pathways: generation and characterization of ustekinumab. Nat Biotechnol 29: 615-624.
39. Leigh IM, Navsaria H, Purkis PE, McKay IA, Bowden PE, et al. (1995) Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro. Br J Dermatol 133: 501-511.
40. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, Whynot J, Novitskaya I, et al. (2007) Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. J Allergy Clin Immunol 119 1210-1217.
41. van Ruissen F, Le M, Carroll JM, van der Valk PG, Schalkwijk J, (1998) Differential effects of detergents on keratinocyte gene expression. J Invest Dermatol 110: 358-363.
42. Kantor AB, Wang W, Lin H, Govindarajan H, Anderle M, et al. (2004) Biomarker discovery by comprehensive phenotyping for autoimmune diseases. Clin Immunol 111: 186-195.
43. Kantor AB, Alters SE, Cheal K, Dietz LJ, (2004) Immune systems biology: immunoprofiling of cells and molecules. Biotechniques 36: 520-524.