Propofol attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production through p38 MAPK and SAPK/JNK in alveolar epithelial cells.

Purpose: Propofol is widely used in sedation and surgical procedures involving patients with acute lung injury (ALI), a common complication in critically ill patients. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in pathological changes in ALI. The present study investigated the anti-inflammatory effect and mechanism of propofol on MCP-1 production and mitogen-activated protein kinase (MAPK) phosphorylation induced by lipopolysaccharide (LPS) in alveolar epithelial cells (AECs).

Methods: AECs were treated with 1 μg/ml LPS for 30 min, 1 h, 6 h, or 24 h following pretreatment with 12.5-100 μM propofol for 30 min. Cytokines and chemokines secretion were profiled using cytokine array, and mRNA and protein levels of MCP-1 were measured by RT-PCR and ELISA. The phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun were measured by Western blot analysis.

Results: Propofol at 50 and 100 μM dose-dependently inhibited MCP-1 mRNA expression (P < 0.05), and also propofol at 50 μM decreased extracellular MCP-1 protein levels (P < 0.05) compared to the LPS group. Propofol at 12.5-50 μM inhibited LPS-induced phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun in AECs.

Conclusions: Propofol at clinically relevant concentrations attenuated LPS-induced MCP-1 mRNA expression and secretion by inhibiting the phosphorylation of p38 MAPK, SAPK/JNK, ATF-2, and c-Jun exerting its anti-inflammatory effects in AECs. These results suggest that propofol may modulate inflammatory response at clinically achievable concentrations in ALI.