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Article Dans Une Revue International Immunopharmacology Année : 2021

Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction

Carmine Rocca
  • Fonction : Auteur
Anna de Bartolo
  • Fonction : Auteur
Fedora Grande
  • Fonction : Auteur
Bruno Rizzuti
Teresa Pasqua
  • Fonction : Auteur
Francesca Giordano
Maria Concetta Granieri
  • Fonction : Auteur
Maria Antonietta Occhiuzzi
  • Fonction : Auteur
Antonio Garofalo
  • Fonction : Auteur
Nicola Amodio
  • Fonction : Auteur
Maria Carmela Cerra
  • Fonction : Auteur
Francis Schneider
Maria Luisa Panno
  • Fonction : Auteur
Marie-Hélène Metz-Boutigue
  • Fonction : Auteur
  • PersonId : 1069882
Tommaso Angelone
  • Fonction : Auteur

Résumé

Global public health is threatened by new pathogens, antimicrobial resistant microorganisms and a rapid decline of conventional antimicrobials efficacy. Thus, numerous medical procedures become life-threating. Sepsis can lead to tissue damage such as myocardium inflammation, associated with reduction of contractility and diastolic dysfunction, which may cause death. In this perspective, growing interest and attention are paid on host defence peptides considered as new potential antimicrobials. In the present study, we investigated the physiological and biochemical properties of Cateslytin (Ctl), an endogenous antimicrobial chromogranin A-derived peptide, in H9c2 cardiomyocytes exposed to lipopolysaccharide (LPS) infection. We showed that both Ctl (L and D) enantiomers, but not their scrambled counterparts, significantly increased cardiomyocytes viability following LPS, even if L-Ctl was effective at lower concentration (1 nM) compared to D-Ctl (10 nM). L-Ctl mitigated LPS-induced LDH release and oxidative stress, as visible by a reduction of MDA and protein carbonyl groups content, and by an increase of SOD activity. Molecular docking simulations strongly suggested that L-Ctl modulates TLR4 through a direct binding to the partner protein MD-2. Molecular analyses indicated that the protection mediated by L-Ctl against LPS-evoked sepsis targeted the TLR4/ERK/JNK/p38-MAPK pathway, regulating NFkB p65, NFkB p52 and COX2 expression and repressing the mRNA expression levels of the LPS-induced proinflammatory factors IL-1β, IL-6, TNF-α and NOS2. These findings indicate that Ctl could be considered as a possible candidate for the development of new antimicrobials strategies in the treatment of myocarditis. Interestingly, L-enantiomeric Ctl showed remarkable properties in strengthening the anti-inflammatory and anti-oxidant effects on cardiomyocytes. Keywords: Antimicrobial peptides; Cardiomyocytes; Cateslytin; Inflammation; Oxidative stress; Toll-like receptor 4.

Domaines

Immunologie
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Dates et versions

hal-03431855 , version 1 (10-03-2023)

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Paternité - Pas d'utilisation commerciale

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Citer

Carmine Rocca, Anna de Bartolo, Fedora Grande, Bruno Rizzuti, Teresa Pasqua, et al.. Cateslytin abrogates lipopolysaccharide-induced cardiomyocyte injury by reducing inflammation and oxidative stress through toll like receptor 4 interaction. International Immunopharmacology, 2021, 94, pp.107487. ⟨10.1016/j.intimp.2021.107487⟩. ⟨hal-03431855⟩
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