Therapeutical potential of a peptide mimicking the SOCS1 kinase inhibitory region in skin immune responses(584 views) Madonna S, Scarponi C, Doti N, Carbone T, Cavani A, Scognamiglio PL, Marasco D, Albanesi C
Keywords: Epidermal Keratinocytes, Ifn-γ-Signaling, Skin Inflammation, Socs1, 3 (2 Acetamidoethyl)thio 6 Ethyl 7 Oxo 1 Azabicyclo[3 2 0]hept 2 Ene 2 Carboxylic Acid, Gamma Interferon, Gamma Interferon Inducible Protein 10, Gamma Interferon Receptor, Hla Dr Antigen, Intercellular Adhesion Molecule 1, Interferon Regulatory Factor 1, Janus Kinase 2, Mitogen Activated Protein Kinase 1, Secondary Lymphoid Tissue Chemokine, Stat1 Protein, Suppressor Of Cytokine Signaling 1, Article, Cell Adhesion, Controlled Study, Enzyme Structure, Epidermis Cell, Human, Human Cell, Immune Response, In Vitro Study, Lymphocyte Migration, Molecular Mimicry, Priority Journal, Protein Analysis, Protein Binding, Protein Domain, Protein Expression, Protein Function, Protein Phosphorylation, T Lymphocyte, Biomimetics, Cell Movement, Cultured, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunoblotting, Immunohistochemistry, Immunoprecipitation, Oligopeptides, Organ Culture Techniques, Rna Interference, Signal Transduction, Suppressor Of Cytokine Signaling Proteins, T-Lymphocytes, Transfection, Cell Movement Drug Effects Immunology, Keratinocytes Drug Effects Immunology, Oligopeptides Immunology Pharmacology, Kir Immunology Metabolism, Signal Transduction Drug Effects Immunology, Skin Drug Effects Immunology, T-Lymphocytes Drug Effects Immunology, Z-Signaling, Ifn-?-Signaling,
Affiliations: *** IBB - CNR ***
Laboratory of Experimental Immunology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Rome, Italy
Institute of Biostructures and Bioimaging, CNR, Naples, Italy
Department of Pharmacy, CIRPEB, University of Naples Federico II, Naples, Italy
References: Eyerich, S., Eyerich, K., Cavani, A., Schmidt-Weber, C., IL-17 and IL-22: siblings, not twins (2010) Trends Immunol., 31, pp. 354-36
Di Meglio, P., Perera, G.K., Nestle, F.O., The multitasking organ: recent insights into skin immune function (2011) Immunity, 35, pp. 857-869
Albanesi, C., Pastore, S., Pathobiology of chronic inflammatory skin diseases: interplay between keratinocytes and immune cells as a target for anti-inflammatory drugs (2010) Curr. Drug. Metab., 11, pp. 210-227
Albanesi, C., Scarponi, C., Cavani, A., Federici, M., Nasorri, F., Girolomoni, G., Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes (2000) J. Invest. Dermatol, 115, pp. 81-87
Lew, W., Bowcock, A.M., Krueger, J.G., Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and "Type 1" inflammatory gene expression (2004) Trends Immunol, 25, pp. 295-305
Lowes, M.A., Bowcock, A.M., Krueger, J.G., Pathogenesis and therapy of psoriasis (2007) Nature, 445, pp. 866-873
Johnson-Huang, L.M., Suárez-Fariñas, M., Pierson, K.C., Fuentes-Duculan, J., Cueto, I., Lentini, T., Sullivan-Whalen, M., A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin (2012) J. Invest. Dermatol., 132, pp. 1177-1187
Federici, M., Giustizieri, M.L., Scarponi, C., Girolomoni, G., Albanesi, C., Impaired IFN-gamma-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1 (2002) J. Immunol, 169, pp. 434-442
Madonna, S., Scarponi, C., De Pità, O., Albanesi, C., Suppressor of cytokine signaling 1 inhibits IFN-gamma inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation (2008) FASEB J, 22, pp. 3287-3297
Yoshimura, A., Naka, T., Kubo, M., SOCS proteins, cytokine signalling and immune regulation (2007) Nat. Rev. Immunol., 7, pp. 454-465
Dimitriou, I.D., Clemenza, L., Scotter, A.J., Chen, G., Guerra, F.M., Rottapel, R., Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins (2008) Immunol. Rev., 224, pp. 265-283
Waiboci, L.W., Ahmed, C.M., Mujtaba, M.G., Flowers, L.O., Martin, J.P., Haider, M.I., Johnson, H.M., Both the suppressor of cytokine signaling 1 [SOCS-1] kinase inhibitory region and SOCS-1 mimetic bind to JAK2 autophosphorylation site: implications for the development of a SOCS-1 antagonist (2007) J. Immunol., 178, pp. 5058-5068
Doti, N., Scognamiglio, P.L., Madonna, S., Scarponi, C., Ruvo, M., Perretta, G., Albanesi, C., New mimetic peptides of the kinase-inhibitory region [KIR] of SOCS1 through focused peptide libraries (2012) Biochem. J, 443, pp. 231-240
Saito, H., Morita, Y., Fujimoto, M., Narazaki, M., Naka, T., Kishimoto, T., IFN regulatory factor-1-mediated transcriptional activation of mouse STAT-induced STAT inhibitor-1 gene promoter by IFN-γ (2000) J. Immunol., 164, pp. 5833-5843
Sestito, R., Madonna, S., Scarponi, C., Cianfarani, F., Failla, C.M., Cavani, A., Girolomoni, G., STAT3-dependent effects of IL-22 in human keratinocytes are counterregulated by sirtuin 1 through a direct inhibition of STAT3 acetylation (2011) FASEB J., 25, pp. 916-927
Albanesi, C., Cavani, A., Girolomoni, G., IL-17 is produced by nickel specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN gamma and TNF-alpha (1999) J. Immunol., 162, pp. 494-502
Paukkonen, K., Naukkarinen, A., Horsmanheimo, M., The development of manifest psoriatic lesions is linked with the appearance of ICAM-1 positivity on keratinocytes (1995) Arch. Dermatol. Res., 287, pp. 165-170
Flowers, L.O., Johnson, H.M., Mujtaba, M.G., Ellis, M.R., Haider, S.M., Subramaniam, P.S., Characterization of a peptide inhibitor of Janus kinase 2 that mimics suppressor of cytokine signaling 1 function (2004) J. Immunol., 172, pp. 7510-7518
Ahmed, C.M., Dabelic, R., Martin, J.P., Jager, L.D., Haider, S.M., Johnson, H.M., Enhancement of antiviral immunity by small molecule antagonist of suppressor of cytokine signaling (2010) J. Immunol, 185, pp. 1103-1113
Ohmori, Y., Hamilton, T.A., The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFN-gamma and TNF-alpha (1995) J. Immunol., 154, pp. 5235-5244
Jaruga, B., Hong, F., Kim, W.H., Gao, B., IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1 (2004) Am. J. Physiol. Gastrointest. Liver Physiol, 287, pp. 1044-1052
Pastore, S., Mascia, F., Mariotti, F., Dattilo, C., Mariani, V., Girolomoni, G., ERK1/2 regulates epidermal chemokine expression and skin inflammation (2005) J. Immunol, 15, pp. 5047-5056
Katiyar, S.K., Matsui, M.S., Elmets, C.A., Mukhtar, H., Polyphenolic antioxidant [-] epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin (1999) Photochem. Photobiol, 69, pp. 148-153
Di Nuzzo, S., Sylva-Steenland, R.M., Koomen, C.W., De Ri, M.A., Da, S.P.K., Bos, J.D., Teunissen, M.B., Exposure to UVB induces accumulation of LFA-1+ T cells and enhanced expression of the chemokine psoriasin in normal human skin (2000) Photochem. Photobiol, 72, pp. 374-382
Cornelius, L.A., Sepp, N., Li, L.J., Degitz, K., Swerlick, R.A., Lawley, T.J., Caughman, S.W., Selective upregulation of intercellular adhesion molecule [ICAM-1] by ultraviolet B in human dermal microvascular endothelial cells (1994) J. Invest. Dermatol, 103, pp. 23-28
Spiekstra, S.W., Toebak, M.J., Sampat-Sardjoepersad, S., van Beek, P.J., Boorsma, D.M., Stoof, T.J., von Blomberg, B.M., Induction of cytokine [interleukin-1alpha and tumor necrosis factor-alpha] and chemokine [CCL20, CCL27, and CXCL8] alarm signals after allergen and irritant exposure (2005) Exp. Dermatol, 14, pp. 109-116
Kwatra, S.G., Dabade, T.S., Gustafson, C.J., Feldman, S.R., JAK inhibitors in psoriasis: a promising new treatment modality (2012) J Drugs Dermatol, 11, pp. 913-918
Punwani, N., Scherle, P., Flores, R., Shi, J., Liang, J., Yeleswaram, S., Levy, R., Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis (2012) J. Am. Acad. Dermatol, 67, pp. 658-664
Abe, R., Yamagishi, S., Fujita, Y., Hoshina, D., Sasaki, M., Nakamura, K., Matsui, T., Topical application of anti-angiogenic peptides based on pigment epithelium-derived factor can improve psoriasis (2010) J. Dermatol. Sci, 57, pp. 183-191
Marasco, D., Perretta, G., Sabatella, M., Ruvo, M., Past and future perspectives of synthetic peptide libraries (2008) Curr. Protein Pept. Sci, 9, pp. 447-467
Therapeutical potential of a peptide mimicking the SOCS1 kinase inhibitory region in skin immune responses
IFN-gamma-activated keratinocytes are key contributors to the pathogenetic mechanisms leading to type-1 immune-mediated skin disorders. In these epidermal cells, SOCS1 negatively regulates the molecular cascades triggered by IFN-gamma by disabling JAK2 phosphorylation through its kinase inhibitory region (KIR). Aimed at potentiating the SOCS1 inhibitory function on JAK2/STAT1 axis in keratinocytes, we recently developed a set of peptides mimicking the SOCS1 KIR domain, which are capable of efficiently binding JAK2 in vitro. Here, the effects of one such SOCS1 KIR mimetic named PS-5 on IFN-gamma-activated human keratinocytes were evaluated. We found that IFN-gamma-activated keratinocytes treated with PS-5 exhibited impaired JAK2, IFN-gammaRalpha, and STAT1 phosphorylation. We also observed reduced levels of the IRF-1 transcription factor, and a strong reduction in ICAM-1, HLA-DR, CXCL10, and CCL2 inflammatory gene expression. ICAM-1 reduced expression resulted in an impaired adhesiveness of T lymphocytes to autologous keratinocytes. Consistently, the migration of T cells toward supernatants from PS-5-treated keratinocytes was drastically reduced. Finally, PS-5 treatment hampered STAT1 activation and the expression of STAT1-dependent inflammatory genes in IFN-gamma-treated explants of human skin. These data collectively indicate that PS-5 has an important therapeutic potential in the treatment of type-1 immune-mediated skin diseases.
Therapeutical potential of a peptide mimicking the SOCS1 kinase inhibitory region in skin immune responses
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Therapeutical potential of a peptide mimicking the SOCS1 kinase inhibitory region in skin immune responses