LL-37 and Citrullinated-LL-37 elicited Transcriptome and Cytokine Profiles in Human Bronchial Epithelial Cells: Citrullination dampens the inflammatory biosignature
Citrullination of LL-37 dampens the inflammatory response in human bronchial epithelial cells compared to LL-37 itself.
Where it sits
this study against the rest of the ll-37 corpusSummary and findings
The study measured the transcriptome and cytokine profiles in human bronchial epithelial cells (HBEC) in response to LL-37 and citrullinated-LL-37 (citLL-37) at a dose of 0.5 μM. It was found that citLL-37 dampened the inflammatory response compared to LL-37. The study identified 118 differentially expressed genes with LL-37 and 71 with citLL-37.
Abstract
<h4>ABSTRACT</h4> The human host defence peptide LL-37 mediates pleiotropic immunomodulatory functions that can be both pro- and anti-inflammatory. Under inflammatory conditions in the lungs, LL-37 is susceptible to the post-translational modification (PTM) citrullination. The impact of this PTM on LL-37’s immunomodulatory functions is not fully understood. Therefore, we characterized the transcriptome and cytokine profile in response to LL-37 and citrullinated-LL-37 (citLL-37), in human bronchial epithelial cells (HBEC). Cells were stimulated with either LL-37 or citLL-37 (0.5 μM), or a scrambled peptide (sLL-37). RNA after 4 hours (h) was analyzed with NanoString nCounter Host Response Panel, and 96 cytokines were examined (after 24 h) in tissue culture supernatants (Luminex platform). Genes and cytokines with a Log2 fold-change ≥0.5 with p <0.05 compared to unstimulated cells were considered differentially expressed (DE). These studies revealed overlapping and distinct biosignatures; There were 118 DE genes with LL-37 and 71 with citLL-37, of which magnitude of change was significantly different for 32 genes. 16 out of 17 DE genes altered by both peptides were directly related to inflammation, and these were significantly less (by ∼45%) with citLL-37 compared to LL-37. Similarly, inflammatory cytokines enhanced in response to LL-37 were significantly less (by 37-94%) with citLL-37. Overall, our findings indicate that citrullination of LL-37 does not abrogate cellular response in HBEC, instead dampens the inflammatory biosignature induced by LL-37.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.