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2017 ; 39
(3
): 549-558
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Neutrophil extracellular traps induce IL-1? production by macrophages in
combination with lipopolysaccharide
#MMPMID28204821
Hu Z
; Murakami T
; Tamura H
; Reich J
; Kuwahara-Arai K
; Iba T
; Tabe Y
; Nagaoka I
Int J Mol Med
2017[Mar]; 39
(3
): 549-558
PMID28204821
show ga
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently
identified type of programmed cell death, and release neutrophil extracellular
traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact
that NETs can trap microorganisms and exhibit bactericidal activity through the
action of NET?associated components. In contrast, the components of NETs have
been recognized as damage?associated molecular pattern molecules (DAMPs), which
trigger inflammatory signals to induce cell death, inflammation and organ
failure. In the present study, to clarify the effect of NETs on cytokine
production by macrophages, mouse macrophage?like J774 cells were treated with
NETs in combination with lipopolysaccharide (LPS) as a constituent of
pathogen?associated molecular patterns. The results revealed that NETs
significantly induced the production of interleukin (IL)?1? by J774 cells in the
presence of LPS. Notably, the NET/LPS?induced IL?1? production was inhibited by
both caspase?1 and caspase?8 inhibitors. Furthermore, nucleases and serine
protease inhibitors but not anti?histone antibodies significantly inhibited the
NET/LPS?induced IL?1? production. Moreover, we confirmed that caspase?1 and
caspase?8 were activated by NETs/LPS, and the combination of LPS, DNA and
neutrophil elastase induced IL?1? production in reconstitution experiments. These
observations indicate that NETs induce the production of IL?1? by J774
macrophages in combination with LPS via the caspase?1 and caspase?8 pathways, and
NET?associated DNA and serine proteases are involved in NET/LPS?induced IL?1?
production as essential components.