Immunomodulatory effects of peptide T on human keratinocyte cells

Tufano, Maria Antonietta; Greco, Rita; Paoletti, Iole; Donnarumma, Giovanna; Canozo, Nunzia; Baroni, Adone

doi:10.1046/j.1365-2133.2002.04915.x

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Our previous studies evidenced the important role played by keratinocytes in justifying the therapeutic activity of PT. The best results were obtained with low concentration of PT, because many peptides at more high concentration show an self‐aggregation, that prevents the correct interaction between the peptide and the specific receptor (7). For this reason, we decided to study the biological behaviour of different peptidomimetics of PT on human keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Where required, 5 × 10 5 cell aliquots were plated in multiwell plates (FALCON, Milan, Italy) and treated with PT (Ala‐Ser‐Thr‐Thr‐Thr‐Asn‐Tyr‐Thr, Sigma) for 24 and 48 h at 10 −8 M as previously described (7) and the peptidomimetics of PT: SVT‐03016 with a molecular weight of 462, SVT‐03017 with a molecular weight of 511, SVT‐03018 with a molecular weight of 492, at different times (24 and 48 h) and at various concentrations (10 −8 and 10 −6 M), as described in the different experiments carried out.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous investigations using human keratinocyte cells treated with PT suggest that these cells play an important role in conditioning the therapeutic effects of the peptide in cutaneous psoriasis (7). Our studies show that PT induces a reduction of ICAM‐1 as well as an overexpression of TGF‐β, HSP70 and α‐v integrin in human keratinocyte cells, and more specifically, the increase of HSP‐70 is modulated by TGF‐β, because anti‐TGF‐β antibodies reduce HSP‐70 overexpression.…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells

Baroni

Paoletti

Greco

et al. 2005

Experimental Dermatology

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Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP-70, TGF-beta, alpha-v integrin, ICAM-1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP-70, TGF-beta and alpha-v integrin than the native peptide. TNF-alpha is overexpressed by PT and SVT-03018; between the other two analogs, SVT-03016 do not produce any significant change in regard to the control, while SVT-03017 shows only a moderate increase in regard to control. SVT-03018 provokes a remarkable upregulation of IL-10, stronger than SVT-03016, SVT-03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM-1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells

Baroni

Paoletti

Greco

et al. 2005

Experimental Dermatology

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Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes

et al. 2013

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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.

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Synthesis and evaluation of diverse analogs of amygdalin as potential peptidomimetics of peptide T

Araya¹,

Rodríguez²,

Rubió³

et al. 2005

Bioorganic & Medicinal Chemistry Letters

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Immunomodulatory effects of peptide T on human keratinocyte cells

Abstract: Our results support the beneficial effect of PT found in vivo, suggesting, moreover, the primary role of keratinocytes upon which PT acts directly by stimulating the anti-inflammatory function and favouring the regeneration of tissue.

Cited by 4 publications

References 31 publications

Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells

Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells

Amygdalin Analogues Inhibit IFN-γ Signalling and Reduce the Inflammatory Response in Human Epidermal Keratinocytes

Synthesis and evaluation of diverse analogs of amygdalin as potential peptidomimetics of peptide T

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