Effects of LL-37 on Gingival Fibroblasts: A Role in Periodontal Tissue Remodeling?

Abstract

Mounting evidence suggests that the host defence peptide, LL-37, plays a role in both inflammation and in wound healing; however, the role of this peptide in the remodeling and maintenance of oral tissues is not yet fully understood. Fibroblasts are the most abundant cell type within the periodontal tissues, and gingival fibroblasts play an important role in maintaining and repairing the gingival tissues which are constantly exposed to external insults. In this study we examined the direct effects of LL-37 treatment on gingival fibroblasts and found that LL-37 significantly increased secretion of both interleukin 8 (IL-8) and IL-6 from these cells. LL-37 tended to decrease matrix metalloproteinase (MMP) activity in gingival fibroblasts, but this decrease did not reach statistical significance. LL-37 significantly increased tissue inhibitor of metalloproteinase-1 (TIMP-1) production by gingival fibroblasts, but had no significant effect on TIMP-2 levels. LL-37 was also shown to significantly increase production of basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF) in gingival fibroblasts. Taken together, these results suggest an important role for the host defence peptide, LL-37, in modulating the fibroblast response to remodeling in periodontal tissues.

Activity of five antimicrobial peptides against periodontal as well as non-periodontal pathogenic strains

“…In addition to their antimicrobial activity some peptides also have other functions i.e. in wound healing, immune modulation or apoptosis [ 10 – 12 ]; some others exhibit anticancer activity [ 13 ].…”

Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, Fusobacterium nucleatum

“…In addition to cytolysis of human erythrocytes, peptoids were tested for their effects on the viability of human primary gingival fibroblasts [ 30 ], since these cells are relevant should peptoids be translated into clinical practice for the treatment of periodontal disease and/or peri-implantitis. Of the seven peptoids tested ( 1 , 3 – 7 and 9 ) all significantly decreased viability of gingival fibroblasts at concentrations of 10 µM and 100 µM, whereas at a concentration of 1 μM, peptoids 4 and 9 were shown not to alter gingival fibroblast viability compared with untreated controls ( Figure 3 ).…”

“…Cultured primary gingival fibroblast cells were obtained with ethical approval and informed consent, and were grown as previously described [ 30 ]. Cells were seeded in 96-well plates at a concentration of 1 × 10 5 cells/mL (100 µL per well).…”

“…In addition to cytolysis of human erythrocytes, peptoids were tested for their effects on the viability of human primary gingival fibroblasts [30], since these cells are relevant should peptoids be translated into clinical practice for the treatment of periodontal disease and/or peri-implantitis. Of the seven peptoids tested (1, 3-7 and…”

Natural Antimicrobials in the Dental Pulp

“…In terms of immunomodulatory roles, LL-37 (and the defensins) can stabilize NETs against bacterial nuclease degradation 37 . Moreover, LL-37 has been shown to have a plethora of actions on oral fibroblasts, including significantly increased production of interleukin 8 (IL-8), IL-6, basic fibroblast growth factor, and hepatocyte growth factor 38 .…”