Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides

Walters, Sheila; Dubey, Vinod S.; Jeffrey, Nicole R; Dixon, Douglas R.

doi:10.1016/j.peptides.2010.06.001

Cited by 30 publications

(27 citation statements)

References 31 publications

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“…LL-37 has been shown to exert antimicrobial activity against oral periodontopathic bacteria, P. gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum (6). It has been reported that LL-37 neutralizes LPS from P. gingivalis and inhibits LPS-induced inflammatory cytokine production (27). The levels of hCAP-18 and LL-37 are increased in the GCF from chronic periodontitis patients (23).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells

et al. 2016

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Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D 3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D 3 and D 2 . Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D 3 .

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Section: Discussionmentioning

confidence: 99%

Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells

et al. 2016

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“…LL-37 attenuates a P. gingivalis extract-induced activation of p38 and ERK responses in human gingival fi broblasts (Inomata et al 2010 ). Modulation of the TLR response by LL-37 occurs at least partly through inhibition of p38 phosphorylation (Walters et al 2010 ).…”

Section: Antimicrobial Peptide Binding To Proinfl Ammatory Agonists Imentioning

confidence: 99%

“…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 …”

Section: Antiinfl Ammatory Activities Ll -37mentioning

confidence: 99%

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

Brogden

Bates

Fischer

2015

Antimicrobial Peptides

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Antimicrobial peptides are well known for their important roles in host defense by enhancing the barrier function and limiting microbial populations of the skin and mucosa. However, many of these peptides are now known to have additional roles assisting innate and adaptive immune functions. To facilitate innate immunity, antimicrobial peptides activate complement, chemoattract cells (e.g., monocytes, macrophages, T cells, neutrophils, immature dendritic cells, and mast cells), enhance phagocytosis, and modulate the production of chemokines and proinfl ammatory cytokines in other cells. At local sites of initiation, antimicrobial peptides can act as opsonins to enhance phagocytosis by monocytes and phagocytes and can activate cells. In the latter, for example, treatment of osteoblasts and osteoblast-like MG63 cells with human beta-defensin (HBD)2 increases their proliferation rates. Treatment of osteoblast-like MG63 cells with HBD2 and HBD3 increases transcript levels of osteogenic markers for differentiation, increases antileukoprotease (ALP) levels, and enhances mineralized nodule formation. To facilitate adaptive immunity, antimicrobial peptides assist the uptake of antigens by monocytes or other antigen-presenting cells and later direct the process toward a Th1 or Th2 adaptive immune response. More commonly though, antimicrobial peptides induce a mixed response characterized by Th1-/Th2-specifi c antibodies and Th1/Th2 cytokines from antigen-exposed splenocytes of immunized animals. Finally, antimicrobial peptides can be detected in the margins around both oral and cutaneous wounds, and there is

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“…Periodontitis is an inflammatory disorder and is initiated by an accumulation of predominantly anaerobic Gram-negative bacteria in subgingival sites. Among the various bacterial species associated with the development of periodontitis, the Gram-negative anaerobic bacterium Porphyromonas gingivalis is one of the most important causative agents of the chronic form of this disease (Walters et al 2010). The outer membrane of P. gingivalis contains lipopolysaccharides that provoke a host immune response that induces interstitial macrophages to release a variety of cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (Pangsomboon et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…For example, Prevotella nigrescens and Staphylococcus aureus isolated from subgingival areas have been shown to produce a bacteriocin that is antagonistic to other periodontal microflora (Kaewsrichan et al 2004). The properties of bacteriocins, i.e., resistance to proteolytic enzymes, a narrow spectrum of antimicrobial activity, and their antagonistic properties (Walters et al 2010;Kaewsrichan et al 2004), could make bacteriocins promising chemotherapeutic agents for the treatment of periodontal infections, and in particular to solve the problems of P. gingivalis re-infections (Yoneda et al 2003). AMPs are usually positively charged (net charge typically between +2 and +9) and are composed of between 12 and 100 amino acids that form an amphipathic structure (Fox et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Novel antimicrobial peptide specifically active against Porphyromonas gingivalis

et al. 2015

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Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, produces a broad spectrum of virulence factors, including outer membrane vesicles, lipopolysaccharides, hemolysins and proteinases. Antimicrobial peptides (AMPs) including bacteriocins have been found to inhibit the growth of P. gingivalis; however, these peptides are relatively large molecules. Hence, it is difficult to synthesize them by a scale-up production. Therefore, this study aimed to synthesize a shorter AMP that was still active against P. gingivalis. A peptide that contained three cationic amino acids (Arg, His and Lys), two anionic amino acids (Glu and Asp), hydrophobic amino acids residues (Leu, Ile, Val, Ala and Pro) and hydrophilic residues (Ser and Gly) was obtained and named Pep-7. Its bioactivity and stability were tested after various treatments. The mechanism of action of Pep-7 and its toxicity to human red blood cells were investigated. The Pep-7 inhibited two pathogenic P. gingivalis ATCC 33277 and P. gingivalis ATCC 53978 (wp50) strains at a minimum bactericidal concentration (MBC) of 1.7 µM, but was ineffective against other oral microorganisms (P. intermedia, Tannerella forsythensis, Streptococcus salivarius and Streptococcus sanguinis). From transmission electron microscopy studies, Pep-7 caused pore formation at the poles of the cytoplasmic membranes of P. gingivalis. A concentration of Pep-7 at four times that of its MBC induced some hemolysis but only at 0.3%. The Pep-7 was heat stable under pressure (autoclave at 110 and 121 °C) and possessed activity over a pH range of 6.8-8.5. It was not toxic to periodontal cells over a range of 70.8-4.4 μM and did not induce toxic pro-inflammatory cytokines. The Pep-7 showed selective activity against Porphyromonas sp. by altering the permeability barriers of P. gingivalis. The Pep-7 was not mutagenic in vitro. This work highlighted the potential for the use of this synthetic Pep-7 against P. gingivalis.

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Antibiotic-induced Porphyromonas gingivalis LPS release and inhibition of LPS-stimulated cytokines by antimicrobial peptides

Cited by 30 publications

References 31 publications

<b>Vitamin D</b><b><sub>3</sub></b><b> analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial </b><b>cells </b>

<b>Vitamin D</b><b><sub>3</sub></b><b> analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial </b><b>cells </b>

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

Novel antimicrobial peptide specifically active against Porphyromonas gingivalis

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