Macrophage Inflammatory Protein-2 in High Mobility Group Box 1 Secretion of Macrophage Cells Exposed to Lipopolysaccharide

Abstract

Background/Aims: Macrophage inflammatory protein-2 (MIP-2), a type of leukocyte chemokine, is primarily produced by macrophages, and levels increase significantly in early inflammation. However, the precise biological functions and mechanisms of MIP-2 in the development of inflammation remain unclear. The purposes of the present study were to investigate the role of MIP-2 in inflammation induced by lipopolysaccharide (LPS) in vitro and to determine the possibility of blocking the high mobility group box 1 (HMGB1) signalling pathway via MIP-2 inhibition. Methods: Macrophage cells (RAW264.7, U937 and THP-1 cells) were divided into control and treatments groups. Expression levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), HMGB1, chemokine (C-C motif) ligand-2 (Ccl-2), Toll-like receptor-4 (TLR-4), inducible nitric oxide synthase (iNOS), phosphorylated MAPKs (p38, ERKs, JNKs), PI3K/Akts, JAKs/STAT3, IκB, and cytoplasmic and nuclear NF-κB p65 in RAW264.7 cells were detected by qRT-PCR, enzyme-linked immunosorbent assay (ELISA) or western blot assays. Results: mip-2 siRNA and an anti-MIP-2 antibody significantly reduced the expression levels of Ccl-2, TLR-4, iNOS, IL-6, IL-1β, HMGB1, and TNF-α in RAW264.7 cells exposed to LPS (P<0.01). Additionally, mRNA expression levels of HMGB1 and TLR-4 in cells treated with LPS+mip-2 siRNA were significantly lower than those in cells treated with LPS alone (P<0.01 or P<0.05). The MIP-2 antibody significantly suppressed activation of p38-MAPK, p-STAT3, and p-Akts and translocation of NF-κB p65 from the cytoplasm to the nucleus in RAW264.7 exposed to LPS (P<0.01 or P<0.05). Conclusion: mip-2 siRNA and the MIP-2 antibody can reduce the inflammatory effects induced by LPS in macrophage cells. The mechanisms may occur through down-regulation of p38-MAPK, STAT3 and Akts phosphorylation and translocation of NF-κB p65. MIP-2 plays an important role in inflammation induced by LPS.

Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-α correlating with high-mobility group box 1 expression in lipopolysaccharides-stimulated RAW 264.7 cells

“…Recent studies have suggested that it exhibits a pronounced proinflammatory effect in the inflammatory response [ 7 ], which is involved in the process of development of sepsis, as well as the important inflammatory mediators for the late period in the lethal effects of LPS [ 8 ]. HMGB1 appears to activate macrophages leading to the secretion of multiple cytokines, which in turn cause extensive inflammatory responses, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nitric oxide [ 9 ].…”

“…Studies have found that propofol can block endotoxin-induced monocyte-macrophages to produce various inflammatory factors [ 3 , 5 , 9 ]. LPS stimulation can induce HMGB1 release from mouse macrophages, however, propofol can inhibit this process leading to downregulation of HMGB1 mRNA and also block the activation of nuclear transcription factor-κB (NF-κB) [ 10 ].…”

Baicalin Inhibits Haemophilus Parasuis-Induced High-Mobility Group Box 1 Release during Inflammation

“…Thus, we chose LPS to induce an inflammation model in piglets. Previous research showed that LPS could induce HMGB1 production in BEAS-2B cells and trigger acute lung injury [ 57 ], and that it stimulated HMGB1 secretion in RAW264.7 cells [ 58 ]. Consistent with previous research, our results indicated that LPS also could trigger HMGB1 production in the piglet.…”

HMGB1 in depression: An overview of microglial HMBG1 in the pathogenesis of depression

“…Binding of HMGB1 to TLR2/TLR4 receptors activates multiple pathways ( Fig. 1 ), including myeloid differentiation factor 88 (MyD88) dependent and independent pathways ( Kang et al, 2014 ),MAPKs( Chaochao et al, 2017 ), nod-like receptor protein 3 (NLRP3) ( Kim et al, 2018 ), ultimately leading to the inflammatory genes’ expression and microglial activation ( Yang et al, 2015b ).…”