The novel human beta‐defensin‐3 is widely expressed in oral tissues

Dunsche, Anton; Açil, Yahya; Dommisch, Henrik; Siebert, Reiner; Schröder, Jens-Michael; Jepsen, Søren

doi:10.1034/j.1600-0722.2002.11186.x

Cited by 172 publications

(175 citation statements)

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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].…”

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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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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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“…β-defensin Four β-defensins (hBD1-4) have been identified and found to be expressed in various epithelial tissues: the trachea, skin, and intestine; and in monocytes and dendritic cells [8,[60][61][62][63][64][65][66][67][68][69]. Like α-defensins, hBDs have three disulphide moieties of cysteine linking residues 1-5, 2-4, and 3-6. hBD1 was first identified in haemodialysate fluid [70] and then from urogenital tissues, skin, intestine, and other tissues [61][62][63][64][65][66][67][68][69]71].…”

Section: Defensinsmentioning

confidence: 99%

“…Like α-defensins, hBDs have three disulphide moieties of cysteine linking residues 1-5, 2-4, and 3-6. hBD1 was first identified in haemodialysate fluid [70] and then from urogenital tissues, skin, intestine, and other tissues [61][62][63][64][65][66][67][68][69]71]. In vitro experiments show that hBD1 is constitutively expressed and that its production is not influenced by bacterial exposure, while other hBDs are inducible when exposed to bacteria [67,[72][73][74][75].…”

Section: Defensinsmentioning

confidence: 99%

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

Komatsuzawa

Ouhara

Yamada

et al. 2005

The Journal of Pathology

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The innate immune system is the primary defence against bacterial infection. Among the factors involved in innate defence, anti-microbial peptides produced by humans have recently attracted attention due to their relevance to some diseases and also to the development of new chemotherapeutic agents. Staphylococcus aureus is one of the major human pathogens, causing a variety of infections from suppurative disease to food poisoning. Methicillin-resistant S. aureus (MRSA) is a clinical problem and with the recent emergence of a vancomycin-resistant strain, this will pose serious problems in the near future. In investigating the molecular biology of S. aureus infections to develop new chemotherapeutic agents against MRSA infections, knowledge of the interaction of innate anti-microbial peptides with S. aureus is important. In vitro and in vivo experiments demonstrate that exposure of S. aureus to host cells can induce the anti-microbial peptides β-defensin-2 (hBD2), hBD3, and LL37/CAP18. The induction level of these peptides differs among strains, as does the susceptibility of the strains, with MRSA strains exhibiting lower susceptibility. In summary, the susceptibility of S. aureus strains, including MRSA strains, to components of the innate immune system varies, with the MRSA strains showing more resistance to both innate immune factors and chemotherapeutic agents.

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“…HBD-3 was further detected in many other tissues such as heart, liver, fetal thymus, and placenta cells (103,105,106). In skin, hBD-3 is stored like hBD-2 in lamellar bodies of keratinocytes (107).…”

Section: Host Defense (Antimicrobial) Peptidesmentioning

confidence: 99%

Host Defense Peptides in Wound Healing

Steinstraesser

Koehler

Jacobsen

et al. 2008

Mol Med

145

112

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Host defense peptides are effector molecules of the innate immune system. They show broad antimicrobial action against gram-positive and -negative bacteria, and they likely play a key role in activating and mediating the innate as well as adaptive immune response in infection and inflammation. These features make them of high interest for wound healing research. Nonhealing and infected wounds are a major problem in patient care and health care spending. Increasing infection rates, growing bacterial resistance to common antibiotics, and the lack of effective therapeutic options for the treatment of problematic wounds emphasize the need for new approaches in therapy and pathophysiologic understanding. This review focuses on the current knowledge of host defense peptides affecting wound healing and infection. We discuss the current data and highlight the potential future developments in this field of research.

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The novel human beta‐defensin‐3 is widely expressed in oral tissues

Cited by 172 publications

References 30 publications

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

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

Innate defences against methicillin‐resistant Staphylococcus aureus (MRSA) infection

Host Defense Peptides in Wound Healing

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