Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887–922) by using a bioinformatics method recently developed by our group. We focused our attention on two variants of the identified HDP, here named r(P)ApoBL and r(P)ApoBS, 38- and 26-residue long, respectively. Both HDPs were found to be endowed with a broad-spectrum antimicrobial activity while they show neither toxic nor haemolytic effects towards eukaryotic cells. Interestingly, both HDPs were found to display a significant anti-biofilm activity, and to act in synergy with either commonly used antibiotics or EDTA. The latter was selected for its ability to affect bacterial outer membrane permeability, and to sensitize bacteria to several antibiotics. Circular dichroism analyses showed that SDS, TFE, and LPS significantly alter r(P)ApoBL conformation, whereas slighter or no significant effects were detected in the case of r(P)ApoBS peptide. Interestingly, both ApoB derived peptides were found to elicit anti-inflammatory effects, being able to mitigate the production of proinflammatory interleukin-6 and nitric oxide in LPS induced murine macrophages. It should also be emphasized that r(P)ApoBL peptide was found to play a role in human keratinocytes wound closure in vitro. Altogether, these findings open interesting perspectives on the therapeutic use of the herein identified HDPs.

Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential / Gaglione, Rosa; Dell'Olmo, Eliana; Bosso, Andrea; Chino, Marco; Pane, Katia; Ascione, Flora; Itri, Francesco; Caserta, Sergio; Amoresano, Angela; Lombardi, Angelina; Haagsman, Hp; Piccoli, Renata; Pizzo, Eliodoro; Veldhuizen, Ej; Notomista, Eugenio; Arciello, Angela. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 130:(2017), pp. 34-50. [10.1016/j.bcp.2017.01.009]

Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential

GAGLIONE, ROSA;DELL'OLMO, ELIANA;BOSSO, ANDREA;CHINO, MARCO;PANE, KATIA;ASCIONE, FLORA;ITRI, FRANCESCO;CASERTA, Sergio;AMORESANO, ANGELA;LOMBARDI, ANGELINA;PICCOLI, RENATA;PIZZO, ELIODORO;NOTOMISTA, EUGENIO;ARCIELLO, ANGELA
2017

Abstract

Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887–922) by using a bioinformatics method recently developed by our group. We focused our attention on two variants of the identified HDP, here named r(P)ApoBL and r(P)ApoBS, 38- and 26-residue long, respectively. Both HDPs were found to be endowed with a broad-spectrum antimicrobial activity while they show neither toxic nor haemolytic effects towards eukaryotic cells. Interestingly, both HDPs were found to display a significant anti-biofilm activity, and to act in synergy with either commonly used antibiotics or EDTA. The latter was selected for its ability to affect bacterial outer membrane permeability, and to sensitize bacteria to several antibiotics. Circular dichroism analyses showed that SDS, TFE, and LPS significantly alter r(P)ApoBL conformation, whereas slighter or no significant effects were detected in the case of r(P)ApoBS peptide. Interestingly, both ApoB derived peptides were found to elicit anti-inflammatory effects, being able to mitigate the production of proinflammatory interleukin-6 and nitric oxide in LPS induced murine macrophages. It should also be emphasized that r(P)ApoBL peptide was found to play a role in human keratinocytes wound closure in vitro. Altogether, these findings open interesting perspectives on the therapeutic use of the herein identified HDPs.
2017
Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential / Gaglione, Rosa; Dell'Olmo, Eliana; Bosso, Andrea; Chino, Marco; Pane, Katia; Ascione, Flora; Itri, Francesco; Caserta, Sergio; Amoresano, Angela; Lombardi, Angelina; Haagsman, Hp; Piccoli, Renata; Pizzo, Eliodoro; Veldhuizen, Ej; Notomista, Eugenio; Arciello, Angela. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 130:(2017), pp. 34-50. [10.1016/j.bcp.2017.01.009]
Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential / Gaglione, Rosa; Dell'Olmo, Eliana; Bosso, Andrea; Chino, Marco; Pane, Katia; Ascione, Flora; Itri, Francesco; Caserta, Sergio; Amoresano, Angela; Lombardi, Angelina; Haagsman, Hp; Piccoli, Renata; Pizzo, Eliodoro; Veldhuizen, Ej; Notomista, Eugenio; Arciello, Angela. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 0006-2952. - 130:(2017), pp. 34-50. [10.1016/j.bcp.2017.01.009]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/666689
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