The neutralising and stimulatory effects of antimicrobial peptide LL-37 in human gingival fibroblasts.
Lappin. M J MJ; Dellett. M M; Mills. K I KI; Lundy. F T FT; Irwin. C R CR
Key Findings
- LL-37 at 1‑10 µg/ml reduced LPS‑induced IL‑6 and CXCL8 production in human gingival fibroblasts
- LL-37 prevented degradation of IκBα, dampening NF‑κB inflammatory signaling
- At 50 µg/ml, LL-37 altered expression of 367 genes, up‑regulating chemokines (CXCL1‑3, CXCL8), IL‑24, CCL2, and SOCS3, and boosted protein levels of CXCL8, HGF, and CXCL1
Practical Outcomes
- Topical or oral‑care products containing LL‑37 or similar peptides might help lower gum inflammation and promote tissue repair. Effective in‑vitro concentrations are around 1‑10 µg/ml, but human safety and delivery methods still need research before real‑world use.
Summary
LL-37, a natural antimicrobial peptide, can calm down gum‑cell inflammation caused by bacterial toxins and also nudges these cells to release healing signals. In lab tests, low‑dose LL-37 (1‑10 µg/ml) cut down key inflammatory molecules, while a higher dose (50 µg/ml) switched on many genes linked to repair and immune signaling.
Abstract
To investigate the effects of LL-37, a broad spectrum antimicrobial peptide expressed in periodontal tissues, on human gingival fibroblast responsiveness to microbial challenge and to explore the direct effects of LL-37 on human gingival fibroblasts. The effect of LL-37 on bacterial lipopolysaccharide-induced expression of Interleukin (IL-6) and chemokine C-X-C motif ligand (CXCL) 8 was determined by enzyme linked immunosorbent assay (ELISA). LL-37's influence on bacterial lipopolysaccharide-induced IκBα degradation was investigated by western blot. DNA microarray analysis initially determined the direct effects of LL-37 on gene expression, these findings were subsequently confirmed by quantitative polymerase chain reaction and ELISA analysis of selected genes. Bacterial lipopolysaccharide-induced IL-6 and CXCL8 production by human gingival fibroblasts was significantly reduced in the presence of LL-37 at concentrations in the range of 1-10 µg/ml. LL-37 led to a reduction in lipopolysaccharide-induced IκBα degradation by Escherichia coli lipopolysaccharide and Porphyromonas gingivalis lipopolysaccharide (10 µg/ml). LL-37 (50 µg/ml) significantly altered the gene expression of 367 genes in human gingival fibroblasts by at least 2-fold. CXCL1, CXCL2, CXCL3, Interleukin-24 (IL-24), CXCL8, Chemokine (C-C motif) Ligand 2, and Suppressor of Cytokine Signalling 3 mRNA were significantly upregulated by LL-37. LL-37 also significantly stimulated expression of CXCL8, hepatocyte growth factor and CXCL1 at the protein level. LL-37 plays an important regulatory role in the immunomodulatory activity of gingival fibroblasts by inhibiting lipopolysaccharide -induced expression of inflammatory cytokines and directly stimulating the expression of an array of bioactive molecules involved in inflammation and repair.
Study Information
pubmed
2023
2023-01-31T00:00:00.000Z
10.1016/j.archoralbio.2023.105634
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