The small antitumoral immune response modifier imiquimod interacts with adenosine receptor signaling in a TLR7- and TLR8-independent fashion

Journal of Investigative Dermatology

Volumn 126, Issue 6, 2006, Pages 1338-1347

  Schön, Michael P ^a   Schön, Margarete ^a   Klotz, Karl Norbert ^b  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; 8 CYCLOPENTYL 1,3 DIPROPYLXANTHINE; ADENOSINE A1 RECEPTOR; ADENOSINE A2A RECEPTOR; ADENOSINE A3 RECEPTOR; ADENOSINE RECEPTOR; ADENOSINE RECEPTOR BLOCKING AGENT; ADENYLATE CYCLASE; CYCLIC AMP; CYTOKINE; FORSKOLIN; IMIDAZOQUINOLINE DERIVATIVE; IMIQUIMOD; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MYELOID DIFFERENTIATION FACTOR 88; RADIOLIGAND; RECEPTOR SUBTYPE; THEOPHYLLINE; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TUMOR NECROSIS FACTOR ALPHA; AMINOQUINOLINE DERIVATIVE; ANTINEOPLASTIC AGENT; IMMUNOLOGICAL ADJUVANT; TLR7 PROTEIN, HUMAN; TLR8 PROTEIN, HUMAN;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; APOPTOSIS; ARTICLE; CELLULAR IMMUNITY; CHO CELL; CONTROLLED STUDY; CYTOKINE RELEASE; DENSITOMETRY; DRUG MECHANISM; DRUG RECEPTOR BINDING; FEEDBACK SYSTEM; FLOW CYTOMETRY; GEL MOBILITY SHIFT ASSAY; HELA CELL; HUMAN; HUMAN CELL; INFLAMMATION; KERATINOCYTE; LEUKEMIA CELL; LIGAND BINDING; MELANOMA CELL; MOUSE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; RECEPTOR AFFINITY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SPLEEN CELL; TUMOR IMMUNITY; ANIMAL; CRICETULUS; DRUG ANTAGONISM; DRUG EFFECT; DRUG POTENTIATION; GENETICS; HAMSTER; METABOLISM; MUTATION; PHYSIOLOGY; TUMOR CELL LINE;

ADJUVANTS, IMMUNOLOGIC; AMINOQUINOLINES; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHO CELLS; CRICETINAE; CRICETULUS; CYTOKINES; HUMANS; MUTATION; NF-KAPPA B; RECEPTORS, PURINERGIC P1; TOLL-LIKE RECEPTOR 7; TOLL-LIKE RECEPTOR 8;

EID: 33745521238     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/sj.jid.5700286     Document Type: Article

References (53)

1. Aggarwal S, Takada Y, Mhashilkar AM, Sieger K, Chada S, Aggarwal BB (2004) Melanoma differentiation-associated gene-7/IL-24 gene enhances NF-kappa B activation and suppresses apoptosis induced by TNF. J Immunol 173:4368-76
2. Bath-Hextall F, Bong F, Perkins W, Williams H (2004) Interventions for basal cell carcinoma of the skin: systematic review. BMJ 329:705
3. Bean MA, Bloom BR, Herberman RB, Old LJ, Oettgen HF, Klein G et al. (1975) Cell-mediated cytotoxicity for bladder carcinoma: evaluation of a workshop. Cancer Res 35:2902-13
4. Beutner KR, Geisse JK, Helman D, Fox TL, Ginkel A, Owens ML (1999) Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 41:1002-7
5. Bong AB, Bonnekoh B, Franke I, Schön MP, Ulrich J, Gollnick H (2002) Imiquimod, a novel immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology 205:135-8
6. Bonizzi G, Karin M (2004) The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25:280-8
7. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106:761-71
8. Bruggen J, Macher E, Sorg C (1981) Expression of surface antigens and its relation to parameters of malignancy in human malignant melanoma. Cancer Immunol Immunother 10:121-7
9. Burns CA, Brown MD (2005) Imiquimod for the treatment of skin cancer. Dermatol Clin 23:151-64
10. Burns R, Ferbel B, Tomai M, Miller R, Gaspari A (2000) The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans cells. Clin Immunol 94:13-23
11. De Lean A, Hancock AA, Lefkowitz RJ (1982) Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes. Mol Pharmacol 21:5-16
12. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of single-stranded RNA. Science 303:1529-31
13. Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527-35
14. Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H et al. (1973) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51:1417-23
15. Gibson SJ, Imbertson LM, Wagner TL (1995) Cellular requirements for cytokine production in response to the immunomodulators imiquimod and S-27609. J Interferon Cytokine Res 15:537-45
16. Gorden KB, Gorski KS, Gibson SJ, Kedl RM, Kieper WC, Qiu X et al. (2005) Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J Immunol 174:1259-68
17. Gupta AK, Cherman AM, Tyring SK (2004) Viral and nonviral uses of imiquimod: a review. J Cutan Med Surg 8:338-52
18. Hannuksela-Svahn A, Nordal E, Christensen OB (2000) Treatment of multiple basal cell carcinomas in the scalp with imiquimod 5% cream. Acta Dermatol Venereol 80:381-2
19. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S et al. (2004) Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 303:1526-9
20. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K et al. (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196-200
21. Holzmann B, Lehmann JM, Ziegler-Heitbrock HW, Funke I, Riethmüller G, Johnson JP (1988) Glycoprotein P3.58, associated with tumor progression in malignant melanoma, is a novel leukocyte activation antigen. Int J Cancer 41:542-7
22. Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdorfer B, Giese T et al. (2002) Quantitative expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J Immunol 168:4531-7
23. Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H et al. (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 3:499
24. Kawai T, Adachi O, Ogawa T, Takeda K, Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11:115-22
25. Klotz KN, Camaioni E, Volpini R, Kachler S, Vittori S, Cristalli G (1999) 2-Substituted N-ethylcarboxamidoadenosine derivatives as high-affinity agonists at human A3 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 360:103-8
26. Klotz KN, Hessling J, Hegler J, Owman C, Kull B, Fredholm BB et al. (1998) Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol 357:1-9
27. Kono T, Kondo S, Pastore S, Shivji GM, Tomai MA, McKenzie RC et al. (1994) Effects of a novel topical immunomodulator, imiquimod, on keratinocyte cytokine gene expression. Lymphokine Cytokine Res 13:71-6
28. Linden J (2001) Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41:775-87
29. Marks R, Gebauer K, Shumack S, Amies M, Bryden J, Fox TL et al. (2001) Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol 44:807-13
30. Megyeri K, Au W-C, Rosztoczy I (1995) Stimulation of interferon and cytokine gene expression by imiquimod and stimulation by Sendai virus utilize similar signal transduction pathways. Mol Cell Biol 15:2207-18
31. Miller RL, Birmachu W, Gibson S (1994) Cytokine induction by imiquimod, preclinical results and pharmacology. Chemother J 4:148-9
32. Montesinos MC, Desai A, Delano D, Chen JF, Fink JS, Jacobson MA et al. (2003) Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum 48:240-7
33. Nguyen DK, Montesinos MC, Williams AJ, Kelly M, Cronstein BN (2003) Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells. J Immunol 171:3991-8
34. Odashima M, Bamias G, Rivera-Nieves J, Linden J, Nast CC, Moskaluk CA et al. (2005) Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterology 129:26-33
35. Ohta A, Sitkovsky MV (2001) Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414:916-20
36. Pauls K, Schön M, Kubitza R, Homey B, Wiesenborn A, Lehmann P et al. (2001) Role of integrin αE(CD103)β7 for tissue-specific epidermal localization of CD8+ T lymphocytes. J Invest Dermatol 117:569-75
37. Reiter MJ, Testerman TL, Miller RL, Weeks CE, Tomai MA (1994) Cytokine induction in mice by the immunomodulator imiquimod. J Leukocyte Biol 55:234-40
38. Schön M, Bong AB, Drewniok C, Herz J, Geilen CC, Reifenberger J et al. (2003) Tumor-selective induction of apoptosis and the small-molecule immune response modifier imiquimod. J Natl Cancer Inst 95:1138-49
39. Schön MP, Schön M (2004) Immune modulation and apoptosis induction: two sides of the antitumoral activity of imiquimod. Apoptosis 9:291-8
40. Schön MP, Wienrich BG, Drewniok C, Bong AB, Eberle J, Geilen CC et al. (2004) Death receptor-independent apoptosis in malignant melanoma induced by the small-molecule immune response modifier imiquimod. J Invest Dermatol 122:1266-76
41. Schulze HJ, Cribier B, Requena L, Reifenberger J, Ferrandiz C, Garcia Diez A et al. (2005) Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol 152:939-47
42. Sidbury R, Neuschler N, Neuschler E, Sun P, Wang XQ, Miller R et al. (2003) Topically applied imiquimod inhibits vascular tumor growth in vivo. J Invest Dermatol 121:1205-9
43. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C et al. (2004) Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu Rev Immunol 22:657-82
44. Stanley MA (1999) Mechanism of action of imiquimod. Papillomavirus Rep 10:23-9
45. Steinmann A, Funk JO, Schuler G, von den Driesch P (2000) Topical imiquimod treatment of a cutaneous melanoma metastasis. J Am Acad Dermatol 43:555-6
46. Stockfleth E, Meyer T, Benninghoff B, Christophers E (2001) Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases. Br J Dermatol 144:1050-3
47. Sullivan GW, Linden J (1998) Role of A2A adenosine receptors in inflammation. Drug Dev Res 45:103-12
48. Suzuki H, Wang B, Shivji GM, Toto P, Amerio P, Tomai MA et al. (2000) Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol 114:135-41
49. Tyring S (2001) Imiquimod applied topically: a novel immune response modifier. Skin Ther Lett 6:1-4
50. Urosevic M, Oberholzer PA, Maier T, Hafner J, Laine E, Slade HB et al. (2004) Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-α? Clin Cancer Res 10:4959-70
51. Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN et al. (2002) N6-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A3 receptor and a starting point for searching A2B ligands. J Med Chem 45:3271-9
52. Wagner TL, Horton VL, Carlson GL (1997) Induction of cytokines in Cynomolgus monkeys by the immune response modifiers, imiquimod, S-27609 and S-28463. Cytokine 9:837-45
53. Weeks CE, Gibson SJ (1994) Induction of interferon and other cytokines by imiquimod and its hydroxylated metabolite R-842 in human blood cells in vitro. J Interferon Cytokine Res 14:81-5