Pancreatitis-Associated Ascitic Fluid Induces Proinflammatory Cytokine Expression in THP-1 Cells by Inhibiting Anti-inflammatory Signaling

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Abstract

Objectives

We investigated whether pancreatitis-associated ascitic fluid (PAAF) could induce the expression of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in THP-1 cells and the mechanism(s) involved.

Methods

THP-1 cells were divided into control and PAAF groups. The PAAF group was incubated with different final concentrations of PAAF, whereas the control group was incubated with culture medium. Effects and mechanisms were determined by measuring the levels of TNF-α and IL-6 mRNA expression; phospho-p38-MAPK, nuclear factor κB, peroxisome proliferator-activated receptor γ activation; and the effect on the inhibitory activity of SB203580 and BAY-117082.

Results

In response to PAAF, overexpression of TNF-α and IL-6 mRNA was found in THP-1 cells compared with those of the corresponding control (P < 0.05), and in a dose-dependent manner. The levels of phospho-p38 and nuclear factor κB p65 were also increased in different PAAF groups, whereas low expression of peroxisome proliferator-activated receptor γ was found compared with the control group (P < 0.05). Furthermore, we presented that the inflammatory response could be partly alleviated by inhibitors SB203580 or BAY-117082, whereas it was markedly inhibited by the simultaneous treatment of 2 inhibitors.

Conclusions

Pancreatitis-associated ascitic fluid up-regulated proinflammatory cytokines by interfering with proinflammatory and anti-inflammatory signaling pathways, thus exacerbating activation in acute pancreatitis.

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