LL-37 Attenuates Production of Pro-inflammatory MCP-1 in Human PDL Cells

Objectives: The human host defense peptide LL-37 plays an important role in the first line of defense against invading microorganisms. LL-37 is produced by white blood cells and kills bacteria through permeabilization of their cell wall causing lysis. LL-37 is cytotoxic to both Gram-positive and Gram-negative bacteria including many strains of oral bacteria. LL-37 also binds the bacterial endotoxin LPS offering another anti-inflammatory mechanism of action. Monocyte chemoattractant protein 1 (MCP-1) promotes recruitment of monocytes and plays a critical role in development and progression of periodontitis. In the present study, we hypothesize that LL-37 directly regulates pro-inflammatory MCP-1 production in human PDL cells.
Methods: PDL cells were obtained from premolars extracted on orthodontic indication. Gene and protein expression were assessed by quantitative real-time RT-PCR and Western blotting, respectively.
Results: Quantitative real-time RT-PCR showed that incubation with LL-37 (1 μM) reduced basal MCP-1 mRNA expression by 40% but had no effect on TNF-α-induced transcript for MCP-1, suggesting that basal and TNF-α-stimulated MCP-1 expression are mediated via different signaling pathways. The same pattern was also observed for IL-6 and GROα (CXCL1) transcripts. LL-37-evoked down-regulation of basal MCP-1 mRNA expression was confirmed on the protein level demonstrated by Western blotting for MCP-1.
Conclusions: We conclude that LL-37 down-regulates basal MCP-1 production in human PDL cells, suggesting that LL-37, besides combating oral pathogens, also acts anti-inflammatory via this mechanism.