Modulation of Macrophage Cell Death, Pyroptosis by Host Defense Peptide LL-37

Abstract

Pyroptosis is defined as a caspase-1 dependent cell death and mainly occurs in macrophages and dendritic cells, accompanied with the release of pro-inflammatory cytokines. Moreover, pyroptosis results in the cellular lysis and release of cytosolic contents, which induce the augmentation of inflammatory reactions. Of note, caspase-1 knockout (KO) causes a protective effect on the sepsis models and improves the survival of mice, in which the IL-1β level was totally suppressed. Thus, caspase-1 activation and possibly pyroptosis play a major role in the mortality of sepsis. AMPs (antimicrobial peptides) are functioning in the first line of defense against invading pathogens. Cathelicidin family of AMPs are recognized in many mammalian species, and LL-37 is the only one human cathelicidin. Besides its broad spectrum of antimicrobial actions, LL-37 has a role in innate immune defense, such as regulation of inflammatory responses and wound healing. Interestingly, LL-37 displays the protective effect on the endotoxemia models. In this review, we introduce a newly identified inhibitory effect of LL-37 on macrophage pyroptosis in vitro and in vivo.