Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice
| Autor: | Johannes Reich, Toshiaki Iba, Isao Nagaoka, Kaori Suzuki, Taisuke Murakami, Kyoko Kuwahara-Arai, Zhongshuang Hu, Hiroshi Tamura |
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| Rok vydání: | 2016 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_treatment Immunology Antimicrobial peptides Caspase 1 Proinflammatory cytokine Cathelicidin Mice 03 medical and health sciences Cathelicidins Sepsis medicine Animals Immunology and Allergy Macrophage Interleukin 6 Original Research Mice Inbred BALB C biology Chemistry Macrophages Pyroptosis General Medicine Macrophage Activation 030104 developmental biology Cytokine biology.protein Cytokines Antimicrobial Cationic Peptides |
| Zdroj: | International Immunology. 28:245-253 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | LL-37 is the only known member of the cathelicidin family of antimicrobial peptides in humans. In addition to its broad spectrum of antimicrobial activities, LL-37 can modulate various inflammatory reactions. We previously revealed that LL-37 suppresses the LPS/ATP-induced pyroptosis of macrophages in vitro by both neutralizing the action of LPS and inhibiting the response of P2X7 (a nucleotide receptor) to ATP. Thus, in this study, we further evaluated the effect of LL-37 on pyroptosis in vivo using a cecal ligation and puncture (CLP) sepsis model. As a result, the intravenous administration of LL-37 improved the survival of the CLP septic mice. Interestingly, LL-37 inhibited the CLP-induced caspase-1 activation and pyroptosis of peritoneal macrophages. Moreover, LL-37 modulated the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in both peritoneal fluids and sera, and suppressed the activation of peritoneal macrophages (as evidenced by the increase in the intracellular levels of IL-1β, IL-6 and TNF-α). Finally, LL-37 reduced the bacterial burdens in both peritoneal fluids and blood samples. Together, these observations suggest that LL-37 improves the survival of CLP septic mice by possibly suppressing the pyroptosis of macrophages, and inflammatory cytokine production by activated macrophages and bacterial growth. Thus, the present findings imply that LL-37 can be a promising candidate for sepsis because of its many functions, such as the inhibition of pyroptosis, modulation of inflammatory cytokine production and antimicrobial activity. |
| Databáze: | OpenAIRE |
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