Amygdalin analogues inhibit IFN-γ signalling and reduce the inflammatory response in human epidermal keratinocytes.
Peptide T (PT), an octapeptide fragment located in the V2 region of the HIV-1 gp120-coating protein, appears to be beneficial in the treatment of psoriasis. Our previous investigations suggest that keratinocytes play a key role in conditioning the therapeutic effects of PT in psoriasis. The aim of this study was to explore the effects of PT and the peptidomimetic natural products, Dhurrin and Prunasin, on the expression of the IL-6, IL-8, IL-23, HSP70 and ICAM-1 on IFN-γ and TNF-α-NHEK activated cells. Moreover, we analysed the interference of PT and its analogues through STAT-3 activation. Our results show that the analogues tested exhibit the beneficial biological effects of PT, suggesting the primary role of keratinocytes upon which PT and the peptidomimetics act directly, by reducing proinflammatory responses. Its reduction appears to be important for therapeutic approach in psoriasis pathogenesis.
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Via Costantinopoli, 16, 80100, Napoli, Italy.
Iole
I
Paoletti
Vincenza
V
De Gregorio
Adone
A
Baroni
Maria Antonietta
MA
Tufano
Giovanna
G
Donnarumma
Juan Jesus
JJ
Perez
D000678:Amygdalin / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism*; D053759:Interleukin-23 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D015717:Peptide T / Q000031:analogs & derivatives / Q000494:pharmacology; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; C508600:IL6 protein, human; D053759:Interleukin-23; D015850:Interleukin-6; D016209:Interleukin-8; D009570:Nitriles; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015717:Peptide T; D018799:Intercellular Adhesion Molecule-1; C019063:prunasin; D000678:Amygdalin; D007371:Interferon-gamma; C011220:dhurrin