LL-37-induced host cell cytotoxicity depends on cellular expression of the globular C1q receptor (p33).

Daniel Svensson, Laura Wilk, Matthias Mörgelin, Heiko Herwald, Bengt-Olof Nilsson

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

21 Citeringar (SciVal)
560 Nedladdningar (Pure)

Sammanfattning

The human host-defense peptide LL-37 not only displays antimicrobial activity but also immune modulating properties that trigger intracellular signaling events in host cells. Since the cytolytic activity of high LL-37 concentrations affects cell viability, the function of LL-37 requires tight regulation. Eukaryotic cells therefore benefit from protective measures to prevent harmful effects of LL-37. p33, also known as globular C1q receptor, is reported to act as an LL-37 antagonist by binding the peptide thereby reducing its cytotoxic activity. In this report, we show that high levels of endogenous p33 correlate with an increased viability in human cells treated with LL-37. Sub-cellular localization analysis showed p33 distribution at the mitochondria, the plasma membrane and in the cytosol. Strikingly, cytosolic over-expression of p33 significantly antagonized detrimental effects of LL-37 on cell fitness, while the reverse effect was observed by siRNA-induced down-regulation of p33. However, modulation of p33 expression had no effect on LL-37-induced plasma membrane pore forming capacity pointing to an intracellular mechanism. A scavenging function of intracellular p33 is further supported by co-immunoprecipitation experiments, showing a direct interaction between intracellular p33 and LL-37. Thus, our findings support an important role of intracellular p33 in maintaining cell viability by counteracting LL-37-induced cytotoxicity.
Originalspråkengelska
Sidor (från-till)87-98
TidskriftThe Biochemical journal
Volym473
DOI
StatusPublished - 2016

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi

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