Abstract

Human -defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2-histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor- (TNF-), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.

Original languageEnglish
Article number1780
JournalInternational Journal of Molecular Sciences
Volume20
Issue number7
Number of pages16
ISSN1422-0067
DOIs
Publication statusPublished - 10 Apr 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • ANTIMICROBIAL PEPTIDES
  • BETA-DEFENSINS
  • CARCINOMA
  • H4 RECEPTOR
  • HISTAMINE H-4 RECEPTOR
  • HUMAN BETA-DEFENSIN-2
  • MAST-CELLS
  • OPMDs
  • TONGUE CANCER
  • bacterial lipopolysaccharide (LPS)
  • histamine
  • histamine H4 receptor
  • human beta defensin 2
  • inflammation
  • mast cells
  • oral cancer
  • oral epithelium
  • oral tongue squamous cell carcinoma
  • 3111 Biomedicine
  • 1182 Biochemistry, cell and molecular biology
  • 116 Chemical sciences

Cite this

@article{5aa3154b840d4bd4a07b6c3dd4131929,
title = "Human β-Defensin 2 Expression in Oral Epithelium: Potential Therapeutic Targets in Oral Lichen Planus",
abstract = "Human -defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2-histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor- (TNF-), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.",
keywords = "ANTIMICROBIAL PEPTIDES, BETA-DEFENSINS, CARCINOMA, H4 RECEPTOR, HISTAMINE H-4 RECEPTOR, HUMAN BETA-DEFENSIN-2, MAST-CELLS, OPMDs, TONGUE CANCER, bacterial lipopolysaccharide (LPS), histamine, histamine H4 receptor, human beta defensin 2, inflammation, mast cells, oral cancer, oral epithelium, oral tongue squamous cell carcinoma, 3111 Biomedicine, 1182 Biochemistry, cell and molecular biology, 116 Chemical sciences",
author = "Abdelhakim Salem and Rabeia Almahmoudi and Jaana Hagstr{\"o}m and Holger Stark and Dan Nordstr{\"o}m and Tuula Salo and Eklund, {Kari K.}",
year = "2019",
month = "4",
day = "10",
doi = "10.3390/ijms20071780",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1422-0067",
publisher = "MDPI",
number = "7",

}

TY - JOUR

T1 - Human β-Defensin 2 Expression in Oral Epithelium

T2 - Potential Therapeutic Targets in Oral Lichen Planus

AU - Salem, Abdelhakim

AU - Almahmoudi, Rabeia

AU - Hagström, Jaana

AU - Stark, Holger

AU - Nordström, Dan

AU - Salo, Tuula

AU - Eklund, Kari K.

PY - 2019/4/10

Y1 - 2019/4/10

N2 - Human -defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2-histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor- (TNF-), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.

AB - Human -defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2-histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor- (TNF-), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP.

KW - ANTIMICROBIAL PEPTIDES

KW - BETA-DEFENSINS

KW - CARCINOMA

KW - H4 RECEPTOR

KW - HISTAMINE H-4 RECEPTOR

KW - HUMAN BETA-DEFENSIN-2

KW - MAST-CELLS

KW - OPMDs

KW - TONGUE CANCER

KW - bacterial lipopolysaccharide (LPS)

KW - histamine

KW - histamine H4 receptor

KW - human beta defensin 2

KW - inflammation

KW - mast cells

KW - oral cancer

KW - oral epithelium

KW - oral tongue squamous cell carcinoma

KW - 3111 Biomedicine

KW - 1182 Biochemistry, cell and molecular biology

KW - 116 Chemical sciences

U2 - 10.3390/ijms20071780

DO - 10.3390/ijms20071780

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 7

M1 - 1780

ER -