The host defense peptide LL‐37 is detected in human parotid and submandibular/sublingual saliva and expressed in glandular neutrophils

Svensson, Daniel; Aidoukovitch, Alexandra; Anders, Emma; Agerberth, Birgitta; Andersson, Fredrik; Ekblad, Eva; Ericson, Dan; Nebel, Daniel; Voss, Ulrikke; Nilsson, Bengt‐Olof

doi:10.1111/eos.12407

Cited by 9 publications

(9 citation statements)

References 31 publications

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“…Based on their findings, DAVIDOPOULOU et al (14) conclude that gingival tissues contribute to the secretion of LL-37, which is in line with our findings showing that salivary epithelial cells contain hCAP18/LL-37. Both isolated human parotid and submandibular/ sublingual saliva contain hCAP18/LL-37, and vascular neutrophils of human parotid and submandibular glands express hCAP18/LL-37, indicating that salivary glands produce hCAP18/LL-37 and deliver it to human whole saliva (16). However, the results of the present study demonstrate that even desquamated oral epithelial cells may provide saliva with hCAP18/LL-37.…”

Section: Discussioncontrasting

confidence: 53%

“…Both isolated human parotid and submandibular/sublingual saliva contain hCAP18/LL‐37, and vascular neutrophils of human parotid and submandibular glands express hCAP18/LL‐37, indicating that salivary glands produce hCAP18/LL‐37 and deliver it to human whole saliva . However, the results of the present study demonstrate that even desquamated oral epithelial cells may provide saliva with hCAP18/LL‐37.…”

Section: Discussioncontrasting

confidence: 50%

“…This antibody detects both the hCAP18 and the LL‐37 immunoreactive bands in western blotting, as demonstrated in Fig. , and has been thoroughly characterized in many previous studies . Hence, the immunoreactive signal observed in the cytoplasm of the desquamated oral epithelial cells may represent either hCAP18 or LL‐37, or both.…”

Section: Resultsmentioning

confidence: 88%

“…LL-37 has been demonstrated in human whole saliva from both adults and children (12)(13)(14)(15), and can also be found in saliva isolated from human parotid and submandibular/sublingual glands, showing that hCAP18/ LL-37 is indeed produced by cells of the major salivary glands (16). It has been reported that LL-37 possesses antibacterial effects against many strains of oral bacteria, including Streptococcus mutans and Porphyromonas gingivalis which are associated with caries and periodontitis (17)(18)(19).…”

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confidence: 99%

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Antimicrobial peptide LL‐37 and its pro‐form, hCAP18, in desquamated epithelial cells of human whole saliva

Aidoukovitch

Dahl

Fält

et al. 2019

European J Oral Sciences

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The antimicrobial peptide LL‐37 is active against oral bacteria and has been demonstrated to be present in human saliva, but its distribution in different fractions of saliva is not known. LL‐37 is formed from its intracellular pro‐form, hCAP18, in an extracellular enzymatic reaction catalyzed by proteinase 3 and kallikrein 5. Here, we prepared cell‐containing and cell‐free fractions of unstimulated human whole saliva by centrifugation after depolymerization of mucins with dithiothreitol, and measured the levels of hCAP18/LL‐37 in these fractions using ELISA. Cellular expression of hCAP18/LL‐37 was determined by western blotting and immunocytochemistry. The ELISA analyses demonstrated that both cells and cell‐free saliva contained hCAP18/LL‐37. Western blot analysis of cell‐pellet homogenates showed a strong band corresponding to hCAP18 at the correct molecular weight and a weak band corresponding to LL‐37. Phase‐contrast and light microscopy revealed that the cells consisted of desquamated epithelial cells. These cells expressed cytoplasmic immunoreactivity for hCAP18/LL‐37. The peripheral part of the cytoplasm, corresponding to the plasma membrane, was particularly rich in hCAP18/LL‐37 immunoreactivity. No immunoreactivity was observed after omission of the primary antibody. We conclude that desquamated epithelial cells of human whole saliva contain antimicrobial hCAP18/LL‐37, suggesting that these cells may take part in the innate immune system by harboring and releasing these peptides.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussioncontrasting

confidence: 50%

Section: Resultsmentioning

confidence: 88%

mentioning

confidence: 99%

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Antimicrobial peptide LL‐37 and its pro‐form, hCAP18, in desquamated epithelial cells of human whole saliva

Aidoukovitch

Dahl

Fält

et al. 2019

European J Oral Sciences

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“…LL-37 shows high expression in neutrophils but also in epithelial cells such as keratinocytes [13]. LL-37 has been detected in human saliva, and interestingly, neutrophils in human salivary glands show high expression of LL-37 [14][15][16][17][18]. Odontoblasts may fulfil an important role in the first line of defence against bacterial invasion.…”

Section: Introductionmentioning

confidence: 99%

Odontoblast-like MDPC-23 cells produce pro-inflammatory IL-6 in response to lipoteichoic acid and express the antimicrobial peptide CRAMP

Odlén

Fält

Dahl

et al. 2019

Acta Odontologica Scandinavica

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Objective: Odontoblasts are thought to be involved in innate immunity but their precise role in this process is not fully understood. Here, we assess effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), produced by Gram-negative and Gram-positive bacteria, respectively, on matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and cathelin-related antimicrobial peptide (CRAMP) expression in odontoblast-like MDPC-23 cells. Material and methods: Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry. Results: Stimulation with LTA (5 and 25 mg/ml) but not LPS (1 and 5 mg/ml) for 24 h enhanced IL-6 mRNA expression. The LTA-induced up-regulation of IL-6 mRNA levels was associated with increased IL-6 protein levels. Stimulation with either LPS or LTA for 24 h lacked effect on both MMP-8 transcript and protein expression. Immunocytochemistry disclosed that MDPC-23 cells expressed immunoreactivity for CRAMP. MDPC-23 cells showed mRNA expression for CRAMP, but stimulation with either LPS or LTA did not modulate CRAMP transcript expression. Conclusions: We show that MDPC-23 cells possess immune-like cell properties such as LTA-induced IL-6 production and expression of the antimicrobial peptide CRAMP, suggesting that odontoblasts may modulate innate immunity via these mechanisms.

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What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)?

Nilsson

2020

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The host defense peptide LL‐37 is detected in human parotid and submandibular/sublingual saliva and expressed in glandular neutrophils

Cited by 9 publications

References 31 publications

Antimicrobial peptide LL‐37 and its pro‐form, hCAP18, in desquamated epithelial cells of human whole saliva

Antimicrobial peptide LL‐37 and its pro‐form, hCAP18, in desquamated epithelial cells of human whole saliva

Odontoblast-like MDPC-23 cells produce pro-inflammatory IL-6 in response to lipoteichoic acid and express the antimicrobial peptide CRAMP

What can we learn about functional importance of human antimicrobial peptide LL-37 in the oral environment from severe congenital neutropenia (Kostmann disease)?

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