Dual role of daphnetin in suppressing HMGB1 release and HMGB1-induced inflammation in murine macrophage RAW264.7 cells and human monocytic THP-1 cells in vitro / 南方医科大学学报
Journal of Southern Medical University
;
(12): 1519-1523, 2015.
Article
in Chinese
| WPRIM
| ID: wpr-232578
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the dual role of daphnetin in suppressing high mobility group box-1 protein (HMGB1) release and blocking HMGB1-induced inflammatory response.</p><p><b>METHODS</b>Murine macrophage RAW264.7 cells were cultured in the presence of daphnetin, lipopolysaccharide (LPS), or both. HMGB1 release from the cells was determined using ELISA, and phosphorylations of JAK1/2 and of STAT1 were detected by Western blotting. Human monocytic THP-1 cells exposed to daphnetin, rhHMGB1, or both were examined for NO production using a NO detection kit, for the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) using ELISA, and for expressions of iNOS, COX-2 and phosphorylated p38, ERK, and JNK with Western blotting.</p><p><b>RESULTS</b>Daphnetin dose-dependently reduced the release of HMGB1 in RAW264.7 cells and suppressed rhHMGB1-induced iNOS and COX-2 expressions and release of TNF-α, IL-6, PGE2, and NO in THP-1 cells. Western blotting revealed that daphnetin significantly down-regulated the phosphorylations of JAK-STAT1 pathway in LPS-stimulated RAW264.7 cells but did not suppress the phosphorylations of MAPKs signaling pathway induced by rhHMGB1 in THP-1 cells.</p><p><b>CONCLUSION</b>Daphnetin can reduce the release of HMGB1 and suppress HMGB1-induced inflammatory response. In RAW264.7 cells, daphnetin inhibited LPS induced HMGB1 release is at least partly mediated by suppressing JAK-STAT1 signaling pathway activation.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Umbelliferones
/
Monocytes
/
Dinoprostone
/
Signal Transduction
/
Cell Line
/
Lipopolysaccharides
/
Interleukin-6
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Tumor Necrosis Factor-alpha
/
HMGB1 Protein
Limits:
Animals
/
Humans
Language:
Chinese
Journal:
Journal of Southern Medical University
Year:
2015
Type:
Article
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