Stat3 is activated in skin lesions by the local application of imiquimod., a ligand of TLR7, and inhibited by the recombinant peptide aptamer rS3-PA

Hormone Molecular Biology and Clinical Investigation

Volumn 10, Issue 2, 2012, Pages 265-272

  Mack, Laura ^a   Brill, Boris ^a   Delis, Natalia ^a   Borghouts, Corina ^a   Weber, Axel ^a   Groner, Bernd ^a  

^a Institute for Biomedical Research   (United Kingdom)

Author keywords

inflammatory skin disease; membrane permeable peptide aptamer; Stat3 inhibition

Indexed keywords

CONCANAVALIN A; IMIQUIMOD; INTERLEUKIN 17; INTERLEUKIN 22; INTERLEUKIN 23; RECOMBINANT PROTEIN; RECOMBINANT STAT3 SPECIFIC PEPTIDE APTAMER; STAT3 PROTEIN; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER CELL; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE RELEASE; FAST PROTEIN LIQUID CHROMATOGRAPHY; FEMALE; IMMOBILIZED METAL AFFINITY CHROMATOGRAPHY; IMMUNE EVASION; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOHISTOCHEMISTRY; INFLAMMATORY CELL; LOCAL THERAPY; MALE; MEMBRANE PERMEABILITY; MOUSE; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN INTERACTION; PSORIASIS; SIGNAL TRANSDUCTION; SKIN CANCER; SKIN DEFECT; TH17 CELL; TOPICAL TREATMENT; TRANSACTIVATION; TREATMENT DURATION; WESTERN BLOTTING;

EID: 85010327966     PISSN: 18681883     EISSN: 18681891     Source Type: Journal    
DOI: 10.1515/hmbci-2012-0007     Document Type: Article

References (37)

1. Groner B., Lucks P., Borghouts C. The function of Stat3 in tumor cells and their microenvironment. Semin Cell Dev Biol 2008;19:341-50.
2. Masciocchi D., Gelain A., Villa S., Meneghetti F., Barlocco D. Signal transducer and activator of transcription 3 (STAT3): a promising target for anticancer therapy. Future Med Chem 2011;3:567-97.
3. Yu H., Pardoll D., Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
4. Kortylewski M., Xin H., Kujawski M., Lee H., Liu Y., Harris T., Drake C., Pardoll D., Yu H. Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 2009;15:114-23.
5. Boniface K., Guignouard E., Pedretti N., Garcia M., Delwail A., Bernard FX., Nau F., Guillet G., Dagregorio G., Yssel H., Lecron JC., Morel F. A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 2007;150:407-15.
6. Akarsu S., Aktan S., Atahan A., Koc P., Ozkan S. Comparison of topical 3% diclofenac sodium gel and 5% imiquimod cream for the treatment of actinic keratoses. Clin Exp Dermatol 2011;36:479-84.
7. Akira S., Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004;4:499-511. “
8. Van Belle AB., de Heusch M., Lemaire MM., Hendrickx E., Warnier G., Dunussi-Joannopoulos K., Fouser LA., Renauld JC., Dumoutier L. IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice. J Immunol 2012;188:462-9.
9. Perera GK., Di Meglio P., Nestle FO. Psoriasis. Annu Rev Pathol 2012;7:385-422.
10. Crawford M., Woodman R., Ko Ferrigno P. Peptide aptamers: tools for biology and drug discovery. Brief Funct Genomic Proteomic 2003;2:72-9.
11. Hoppe-Seyler F., Crnkovic-Mertens I., Tomai E., Butz K. Peptide aptamers: specific inhibitors of protein function. Curr Mol Med 2004;4:529-38.
12. Nagel-Wolfrum K., Buerger C., Wittig I., Butz K., Hoppe-Seyler F., Groner B. The interaction of specific peptide aptamers with the DNA binding domain and the dimerization domain of the transcription factor Stat3 inhibits transactivation and induces apoptosis in tumor cells. Mol Cancer Res 2004;2: 170-82.
13. Borghouts C., Kunz C., Delis N., Groner B. Monomeric recom-binant peptide aptamers are required for efficient intracellular uptake and target inhibition. Mol Cancer Res 2008;6:267-81.
14. Schöneberger H., Weiss A., Brill B., Delis N., Borghouts C., Groner B. The integration of a Stat3 specific peptide aptamer into the thioredoxin scaffold protein strongly enhances its inhibitory potency. Horm Mol Biol Invest 2011;5:9.
15. Borghouts C., Delis N., Brill B., Weiss A., Mack L., Lucks P., Groner B. A membrane penetrating peptide aptamer inhibits Stat3 function and suppresses the growth of Stat3 addicted tumor cells. JAK-STAT 2012;1:1-11.
16. van der Fits L., Mourits S., Voerman JS., Kant M., Boon L., Laman JD., Cornelissen F., Mus AM., Florencia E., Prens EP., Lubberts E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 2009;182:5836-45.
17. Desai T., Chen CL., Desai A., Kirby W. Basic pharmacology of topical imiquimod., 5-fluorouracil, and diclofenac for the derma-tologic surgeon. Dermatol Surg 2012;38:97-103.
18. Jarnicki A., Putoczki T., Ernst M. Stat3: linking inflammation to epithelial cancer-more than a “gut” feeling? Cell Div 2010;5:14.
19. Nakajima K., Kanda T., Takaishi M., Shiga T., Miyoshi K., Nakajima H., Kamijima R., Tarutani M., Benson JM., Elloso MM., Gutshall LL., Naso MF., Iwakura Y., DiGiovanni J., Sano S. Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol 2011;186:4481-9.
20. Bowcock AM., Krueger JG. Getting under the skin: the immuno-genetics of psoriasis. Nat Rev Immunol 2005;5:699-711.
21. Johnson-Huang LM., McNutt NS., Krueger JG., Lowes MA. Cytokine-producing dendritic cells in the pathogenesis of inflammatory skin diseases. J Clin Immunol 2009;29:247-56.
22. Gottlieb AB. Psoriasis: emerging therapeutic strategies. Nat Rev Drug Discov 2005;4:19-34.
23. Tremezaygues L., Reichrath J. Vitamin D analogs in the treatment of psoriasis: where are we standing and where will we be going? Dermatoendocrinol 2011 ;3: 180-6.
24. Sano S., Chan KS., Carbajal S., Clifford J., Peavey M., Kiguchi K., Itami S., Nickoloff BJ., DiGiovanni J. Stat3 links activated_ keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11: 43-9.
25. Li AG., Wang D., Feng XH., Wang XJ. Latent TGFbeta1 overex-pression in keratinocytes results in a severe psoriasis-like skin disorder. EMBO J 2004;23:1770-81.
26. Gudjonsson JE., Johnston A., Dyson M., Valdimarsson H., Elder JT. Mouse models of psoriasis. J Invest Dermatol 2007;127:1292-308.
27. Pasparakis M., Courtois G., Hafner M., Schmidt-Supprian M., Nenci A., Toksoy A., Krampert M., Goebeler M., Gillitzer R., Israel A., Krieg T., Rajewsky K., Haase I. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 2002;417:861-6.
28. Chan JR., Blumenschein W., Murphy E., Diveu C., Wiekowski M., Abbondanzo S., Lucian L., Geissler R., Brodie S., Kimball AB., Gorman DM., Smith K., de Waal Malefyt R., Kastelein RA., McClanahan TK., Bowman EP. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med 2006;203: 2577-87.
29. Zheng Y., Danilenko DM., Valdez P., Kasman I., Eastham-Anderson J., Wu J., Ouyang W. Interleukin-22, a T(H)17 cytokine., mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445:648-51.
30. Wagner EF., Schonthaler HB., Guinea-Viniegra J., Tschachler E. Psoriasis: what we have learned from mouse models. Nat Rev Rheumatol 2010;6:704-14.
31. Annunziato F., Cosmi L., Liotta F., Maggi E., Romagnani S. Type 17 T helper cells-origins, features and possible roles in rheumatic disease. Nat Rev Rheumatol 2009;5:325-31.
32. Bolon B. Cellular and molecular mechanisms of autoimmune disease. Toxicol Pathol. Epub 2011 Nov 21.
33. Lubberts E. IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 2008;41:84-91.
34. McGeachy MJ., Cua DJ. Th17 cell differentiation: the long and winding road. Immunity 2008;28:445-53.
35. Zenewicz LA., Flavell RA. IL-22 and inflammation: leukin' through a glass onion. Eur J Immunol 2008;38:3265-8.
36. Harris TJ., Grosso JF., Yen HR., Xin H., Kortylewski M., Albesiano E., Hipkiss EL., Getnet D., Goldberg MV., Maris CH., Housseau F., Yu H., Pardoll DM., Drake CG. Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 2007; 179: 4313-7.
37. Miyoshi K., Takaishi M., Nakajima K., Ikeda M., Kanda T., Tarutani M., Iiyama T., Asao N., DiGiovanni J., Sano S. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. J Invest Dermatol 2011;131:108-17.