On March 2, 2021, Biswas, Debabrata; Ambalavanan, Poornima; Ravins, Miriam; Anand, Aparna; Sharma, Abhinay; Lim, Kimberly Xuan Zhen; Tan, Rachel Ying Min; Lim, Hwee Ying; Sol, Asaf; Bachrach, Gilad; Angeli, Veronique; Hanski, Emanuel published an article.Category: piperazines The title of the article was LL-37-mediated activation of host receptors is critical for defense against group A streptococcal infection. And the article contained the following:
Group A Streptococcus (GAS) causes diverse human diseases, including life-threatening soft-tissue infections. It is accepted that the human antimicrobial peptide LL-37 protects the host by killing GAS. Here, we show that GAS extracellular protease ScpC N-terminally cleaves LL-37 into two fragments of 8 and 29 amino acids, preserving its bactericidal activity. At sub-bactericidal concentrations, the cleavage inhibits LL-37-mediated neutrophil chemotaxis, shortens neutrophil lifespan, and eliminates P2X7 and EGF receptors ‘ activation. Mutations at the LL-37 cleavage site protect the peptide from ScpC-mediated splitting, maintaining all its functions. The mouse LL-37 ortholog CRAMP is neither cleaved by ScpC nor does it activate P2X7 or EGF receptors. Treating wild-type or CRAMP-null mice with sub-bactericidal concentrations of the non-cleavable LL-37 analogs promotes GAS clearance that is abolished by the administration of either P2X7 or EGF receptor antagonists. We demonstrate that LL-37-mediated activation of host receptors is critical for defense against GAS soft-tissue infections. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Category: piperazines
The Article related to host receptor ll37 activation defense streptococcal infection, cramp, egfr, gas, ll-37, p2x7r, group a streptococcus, host-defense peptides, innate immunity, murine models of human gas soft-tissue infections, neutrophils and other aspects.Category: piperazines
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