Upregulation of Human Beta-Defensin 2 Peptide Expression in Oral Lichen Planus, Leukoplakia and Candidiasis. An Immunohistochemical Study

Abiko, Yoshihiro; Jinbu, Yoshinori; Noguchi, Tadahide; Nishimura, Michiko; Kusano, Kanichi; Amaratunga, Prasad; Shibata, Toshiyuki; Kaku, Tohru

doi:10.1078/0344-0338-00298

Cited by 46 publications

(24 citation statements)

References 13 publications

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“…As predicted by the protamine results, this mutant also had increased susceptibility to human ␤-defensin 2 (Fig. 5), which is made by oral epithelial cells (1,29,39), All defects of the yck2/yck2 mutant were due to the insertions in YCK2 because complementing this mutant with a wildtype copy of YCK2 restored the wild-type phenotype in all assays. Collectively, these results suggest that in C. albicans, The wild-type control strain was DAY185.…”

Section: Interactions Of C Albicans With Oral Epithelial Cells and Ementioning

confidence: 89%

Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

et al. 2009

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Candida albicans interacts with oral epithelial cells during oropharyngeal candidiasis and with vascular endothelial cells when it disseminates hematogenously. We set out to identify C. albicans genes that govern interactions with these host cells in vitro. The transcriptional response of C. albicans to the FaDu oral epithelial cell line and primary endothelial cells was determined by microarray analysis. Contact with epithelial cells caused a decrease in transcript levels of genes related to protein synthesis and adhesion, whereas contact with endothelial cells did not significantly influence any specific functional category of genes. Many genes whose transcripts were increased in response to either host cell had not been previously characterized. We constructed mutants with homozygous insertions in 22 of these uncharacterized genes to investigate their function during host-pathogen interaction. By this approach, we found that YCK2, VPS51, and UEC1 are required for C. albicans to cause normal damage to epithelial cells and resist antimicrobial peptides. YCK2 is also necessary for maintenance of cell polarity. VPS51 is necessary for normal vacuole formation, resistance to multiple stressors, and induction of maximal endothelial cell damage. UEC1 encodes a unique protein that is required for resistance to cell membrane stress. Therefore, some C. albicans genes whose transcripts are increased upon contact with epithelial or endothelial cells are required for the organism to damage these cells and withstand the stresses that it likely encounters during growth in the oropharynx and bloodstream.

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Section: Interactions Of C Albicans With Oral Epithelial Cells and Ementioning

confidence: 89%

Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

et al. 2009

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“…HBD-1 is constitutively expressed, and may be modulated by inflammation. HBD-2 and HBD-3 are inducible in cells with stimulation by pro-inflammatory cytokines such as IL-1beta, TNF-alpha, IFN-gamma and microorganisms 2,14) . Therefore, HBD-1 may influence normal epithelial interactions with the commensal flora, and HBD-2 and HBD-3 may participate in the host defense response to enteric microbes.…”

Section: Introductionmentioning

confidence: 99%

Age-related Differences in Localization of Beta-defensin-2 in Human Gingival Epithelia

Matsuzaka

Sato

Ishihara

et al. 2006

Bull. Tokyo Dent. Coll.

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Defensins are known to play an important role in defense against bacteria. It is also known that immunity against infection is compromised with age. The purpose of this study was to evaluate the localization of human beta-defensin (HBD)-2 in human gingival epithelia according to age. Gingival epithelia in maxillary premolar buccal normal regions was immunohistochemically stained for HBD-2. Specimens were divided into two groups: 6 cases in a young group (Ͻ20 years old) and 7 cases in an elderly group (Ͼ50 years old). Expression of HBD-2 in gingival epithelium in young subjects was mostly detected in the superficial layer of the parakeratinized layer, while some areas of the spinous cell layer in elderly subjects were positive for HBD-2, as was the superficial layer. Two cases in the young group and 5 cases in the elderly group immunoreacted with HBD-2 in the spinous cell layer. Furthermore, immunoreaction was stronger in the elderly group. The results revealed HBD-2 positive cells in spinous cells in the elderly group and in the parakeratinized layer in the young group.

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“…Bacteria and cytokines IL-1 and TNFα upregulate HBD-2 expression in lung and skin epithelial cells [10,28] and induction of HBDs by these stimuli is differentially regulated involving multiple mechanisms [29]. Expression of HBDs in oral tissues has also been extensively studied [23,[30][31][32][33][34][35][36][37][38][39][40]. In gingival epithelium, variable expression levels of HBD-1, -2 or -3 are found in either healthy or diseased gingival tissues [41,42] Previously, we transduced a number of non-HBD-2-expressing cell lines to produce HBD-2 with the notion that these cells may become part of the innate defense mechanisms against infection [6,49].…”

mentioning

confidence: 99%

Capacity of human β-defensin expression in gene-transduced and cytokine-induced cells

Yin¹,

Dang²,

Zhang³

et al. 2006

Biochemical and Biophysical Research Communications

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The purpose of this study was to determine the capacity of cells transduced with human β-defensins (HBDs) to express antimicrobial peptides, since sufficient expression level is required for effective antimicrobial activity. Retroviral vector pBabeNeo and lentiviral vector SIN18cPPTRhMLV (SIN18) carrying HBDs were utilized to transduce non-HBD-expressing cells such as fibroblasts or HBD-producing oral epithelial cells. We found that HBD-3 gene transfer to fibroblasts was possible not via retrovirus but by direct vector transfection. SIN18 had high transduction efficiencies (80.9-99.9%) and transduced cells expressed higher amounts of HBD-2 than those by pBabe-Neo. Primary human gingival epithelial cells (HGECs) expressed greater amounts of HBD-2 than primary fibroblasts after lentiviral transduction. Additionally, HBD-2 secretion from transduced HGECs cells was further increased when stimulated with IL-1 or TNFα. Our data indicate that while HBD-2 expression is limited in primary fibroblasts, its expression in HGECs may be maximized by gene transduction plus cytokine induction. KeywordsHBD-2; HBD-3; Lentiviral vectors; Retroviral vectors; IL-1; TNFα; Gingival epithelial cells Natural antimicrobial peptides have been considered as an alternative option for infection control due to the increasing resistance of microbes to conventional antibiotics. Because some potent antimicrobial peptides are encoded by single genes, the possibility of artificially delivering these genes into tissues/organs to augment innate immunity against infection or creating transgenic animals to produce antimicrobial peptides has been explored [1][2][3][4][5]. Subsequently, the term antimicrobial gene therapy has emerged [6] and engineered skin NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript models have been used to test the concept of antimicrobial gene therapy both in vitro and in vivo [7,8]. Human β-defensins (HBDs or DEFB) and cathelicidin LL37 are being actively used as study models for their potent ability to kill a broad spectrum of bacteria and fungi [6,7,[9][10][11][12][13], as well as to inhibit viral infections [14,15]. HBDs are expressed mostly in epithelia [11,12,[16][17][18][19][20][21][22][23][24]. Besides the cloned, sequenced, and well-characterized HBD-1, -2, -3, and -4, there appears to be at least 28 more HBDs existing based on the genomic surveys using computational search strategy [25][26][27]. Fourteen HBDs or DEFB gene transcripts (DEFB-1, -4, and DEFB-103 to -114) were investigated using reverse transcriptionpolymerase chain reaction (RT-PCR) to detect their expression in gingival keratinocytes and a selected few have been classified as constitutive or inducible [27].HBDs are considered to play an important role in epithelial defense mechanism and the regulation of their expression in diseased conditions is being actively investigated. Bacteria and cytokines IL-1 and TNFα upregulate HBD-2 expression in lung and skin epithelial cells [10,28] and induction of HBDs by these stimuli is...

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Upregulation of Human Beta-Defensin 2 Peptide Expression in Oral Lichen Planus, Leukoplakia and Candidiasis. An Immunohistochemical Study

Cited by 46 publications

References 13 publications

Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

Age-related Differences in Localization of Beta-defensin-2 in Human Gingival Epithelia

Capacity of human β-defensin expression in gene-transduced and cytokine-induced cells

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