Transcription profiling of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37

The objective of the study was to evaluate transcriptional response of endotoxin-stimulated human monocytic cells in presence and absence of host defense peptide LL-37. A functional genomics approach was used to establish a temporal transcriptional profile and identify differentially expressed genes in LPS (100ng/ml)-stimulated human monocytic THP-1 cells, in the presence or absence of LL-37 (20ug/ml) after 1, 2, 4 and 24 hrs of stimulation. The peptide significantly inhibited the expression of LPS-induced pro-inflammatory genes regulated by NF-kappa B, such as NF-kappa B1 (p105/p50) and TNF-alpha-induced protein 2 (TNFAIP2). In contrast, LL-37 did not significantly inhibit LPS-induced genes that antagonize inflammation, such as TNF-alpha-induced protein 3 (TNFAIP3) and the NF-kappa B inhibitor, NF-kappa BIA, or genes involved in cell movement and recruitment (chemokines). The trends of gene expression were further validated by quantitative real-time PCR. This study implicates that LL-37 plays a role in the delicate balancing act of inflammatory responses.