Hu, Zhongshuang and Murakami, Taisuke and Suzuki, Kaori and Tamura, Hiroshi and Reich, Johannes and Kuwahara-Arai, Kyoko and Iba, Toshiaki and Nagaoka, Isao (2016) Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice. INTERNATIONAL IMMUNOLOGY, 28 (5). pp. 245-253. ISSN 0953-8178, 1460-2377
Full text not available from this repository. (Request a copy)Abstract
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 P2X(7) (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-1 beta, IL-6 and TNF-alpha) in both peritoneal fluids and sera, and suppressed the activation of peritoneal macrophages (as evidenced by the increase in the intracellular levels of IL-1 beta, IL-6 and TNF-alpha). 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; CELL-DEATH; INFLAMMATORY RESPONSE; SEPSIS; APOPTOSIS; SHOCK; IL-1; ATP; LPS; LIPOPOLYSACCHARIDE; caspase-1; cecal ligation and puncture; cytokines; IL-1 beta; sepsis |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2019 10:23 |
| Last Modified: | 22 Mar 2019 10:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2982 |
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