A murine cellular model of necroinflammation displays RAGE-dependent cytokine induction that connects to hepatoma cell injury.

Journal of Cellular and Molecular Medicine
Malte BachmannHeiko Mühl

Abstract

Unresolved inflammation maintained by release of danger-associated molecular patterns, particularly high-mobility group box-1 (HMGB1), is crucial for hepatocellular carcinoma (HCC) pathogenesis. To further characterize interactions between leucocytes and necrotic cancerous tissue, a cellular model of necroinflammation was studied in which murine Raw 264.7 macrophages or primary splenocytes were exposed to necrotic lysates (N-lys) of murine hepatoma cells or primary hepatocytes. In comparison to those derived from primary hepatocytes, N-lys from hepatoma cells were highly active-inducing in macrophages efficient expression of inflammatory cytokines like C-X-C motif ligand-2 , tumor necrosis factor-α, interleukin (IL)-6 and IL-23-p19. This activity associated with higher levels of HMGB1 in hepatoma cells and was curbed by pharmacological blockage of the receptor for advanced glycation end product (RAGE)/HMGB1 axis or the mitogen-activated protein kinases ERK1/2 pathway. Analysis of murine splenocytes furthermore demonstrated that N-lys did not comprise of functionally relevant amounts of TLR4 agonists. Finally, N-lys derived from hepatoma cells supported inflammatory splenic Th17 and Th1 polarization as detected by IL-17, IL-22 o...Continue Reading

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Citations

Apr 15, 2021·Seminars in Immunopathology·Jöran LückeSamuel Huber

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Methods Mentioned

BETA
FCS
PMA
PCR
ELISA

Software Mentioned

Sequence Detector
GraphPad

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