Kupffer cell-derived TNF-? promotes hepatocytes to produce CXCL1 and mobilize
neutrophils in response to necrotic cells
#MMPMID29476069
Su L
; Li N
; Tang H
; Lou Z
; Chong X
; Zhang C
; Su J
; Dong X
Cell Death Dis
2018[Feb]; 9
(3
): 323
PMID29476069
show ga
The damage-associated molecular pattern molecules (DAMPs) released by necrotic
cells can trigger inflammatory response, which will facilitate the clearance of
these dead cells. Neutrophil mobilization is a very important step for the dead
cell clearance, however the detailed mechanisms for DAMPs induce neutrophil
mobilization remains largely elusive. In this study, by using a necrotic
cell-induced neutrophil mobilization mice model, we found that both neutrophil
number and percentage rapidly (as early as 30 min) increased with necrotic cells
but not live cell treatment. CXCL1 was rapidly increased in the serum and was
responsible for the neutrophil mobilization when treated with necrotic cells. We
further demonstrated that the hepatocytes in the liver were the main source of
CXCL1 production in response to necrotic cells challenge. However, the
hepatocytes did not express CXCL1 when incubating with necrotic cells alone. When
Kupffer cells were ablated, the increased CXCL1 levels as well as neutrophil
mobilization were abolished with necrotic cells challenge. Moreover, we clarified
Kupffer cells-derived TNF-? activates the NF-?B pathway in hepatocytes and
promote hepatocytes to express CXCL1. In summary, we showed that the liver is the
main source for necrotic cell-induced CXCL1 production and neutrophil
mobilization. Kupffer cells in the liver sense DAMPs and release TNF-? to
activate the NF-?B pathway in hepatocytes. The interaction between Kupffer cells
and hepatocytes is critical for CXCL1 production.
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