Suppressive effect of the antimicrobial peptide LL‐37 on expression of IL‐6, IL‐8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts

Abstract

Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL-37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL-37 did not alter these responses. However, LL-37 was able to suppress the killed P. gingivalis cell-induced secretion of interleukin (IL)-6 and IL-8. LL-37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol-water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL-37 can exert a suppressive effect on P. gingivalis-induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL-37 in vivo.

LL-37 Concentrations and the Relationship to Vitamin D, Immune Status, and Inflammation in HIV-Infected Children and Young Adults

“…Thus, it is reasonable to think that LL-37 and IL-6 interact with one another or one affects the other in HIV. In fact, this relationship has been previously demonstrated in other populations 40 and in vitro. 41 This is an important finding that deserves further investigation, including evaluating functional links between IL-6 and LL-37.…”

<i><b>Porphyromonas gingivalis</b></i><b>-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial </b><b>cells </b>

“…LL-37 deficiency has been directly implicated in the development of periodontitis (24). Moreover, LL-37 suppresses IL-6, IL-10, and CXCL10 production induced by heat-killed P. gingivalis in human gingival fibroblasts in a paracrine manner (12). The expression of hCAP-18/LL-37 in GCF and saliva obtained from patients with chronic periodontitis is higher than that IL-33 down-regulates the induction of hCAP-18/LL-37 production in human gingival epithelial cells, implying that IL-33 attenuates antimicrobial immune responses by gingival epithelial cells against bacterial mucosal infections.…”

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

“…Attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in macrophages (Scott et al 2000 ), lung epithelial cells (Scott et al 2000 ), peripheral blood mononuclear cells (Molhoek et al 2009 ), and whole blood leukocytes (Walters et al 2010 ) Attenuates MAPK pathway activation of p38 and ERK responses in gingival fi broblasts (Inomata et al 2010 ) α -defensins Inhibit the production of proinfl ammatory cytokines from macrophages (Miles et al 2009 ) Attenuate a chemokine and proinfl ammatory cytokine response in mice (Kohlgraf et al 2010 ) β -defensins HBD3 attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in dendritic cells (Pingel et al 2008 ;Harvey et al 2013 ), in THP-1 human myelomonocytic cells (Semple et al 2010 ), peripheral blood monocyte-derived macrophages (Semple et al 2010 ), and in RAW264.7 murine macrophages (Semple et al 2010 ) DEFB114 attenuates MAPK pathway p42/44 response and attenuates an agonist-induced TNF-α response in RAW264.7 murine macrophages (Yu et al 2013 ) DEFB123 attenuates an agonist-induced MAPK pathway activation of p42/44 and p38 and attenuates an agonist-induced TNF-α response in RAW264.7 murine macrophages (Motzkus et al 2006 ) DEFB126 attenuates an agonist-induced proinfl ammatory response in RAW264.7 murine macrophages (Liu et al 2013a ) Attenuate a chemokine and proinfl ammatory cytokine response in mice (Kohlgraf et al 2010 ) θ-defensins Retrocyclin RTD-1 attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in human peripheral blood leukocytes (Schaal et al 2012 …”