Inhibition of hBD-3, but Not hBD-1 and hBD-2, mRNA Expression by Corticosteroids

Duits, L. A.; Rademaker, Mirjam; Ravensbergen, Bep; Sterkenburg, M. A. J. A. Van; Strijen, Elizabeth van; Hiemstra, Pieter S.; Nibbering, Peter H.

doi:10.1006/bbrc.2000.4157

Cited by 54 publications

(37 citation statements)

References 24 publications

(25 reference statements)

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“…Our findings regarding the effects of dexamethasone are in agreement with those of Tomita et al who found that LPS-induced upregulation of hBD-2 mRNA was inhibited by dexamethasone in a human airway cell line (48), which is relevant due to the high homology between hBD-2 and TAP genes (4) and their similar regulation by inflammatory mediators (13). Conversely, Duits et al reported no effect of dexamethasone on hBD-1 or hBD-2 expression, whereas basal and induced hBD-3 mRNA expression was inhibited by dexamethasone in primary bronchial epithelial cells (16). Reasons for this discrepancy are not clear, but considering our finding that dexamethasone did not significantly affect the LPS-induced upregulation of LAP, it seems likely that expression of each ␤-defensin is regulated somewhat independently, as has been shown for their pathogen-specific induction in humans (34).…”

Section: Discussionmentioning

confidence: 99%

Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells

et al. 2007

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Susceptibility to bacterial pneumonia in cattle is enhanced by stressors such as transportation, weaning, and commingling, which trigger a physiologic stress response resulting in elevated levels of endogenous corticosteroids and catecholamines. To determine the effect of neuroendocrine mediators on the expression of innate defense peptides in the lung, bovine tracheal epithelial cells were exposed to dexamethasone, catecholamines, acetylcholine, or substance P, and then ␤-defensin expression was quantified using real-time reverse transcription-PCR. Basal expression of tracheal antimicrobial peptide (TAP) mRNA was not affected by any of the mediators tested. However, induction of TAP expression by lipopolysaccharide was significantly inhibited by pretreatment with dexamethasone. Bronchial biopsy specimens from dexamethasone-treated calves had significantly lower expression of TAP and lingual antimicrobial peptide (LAP) mRNA than saline-treated controls following 48 h of treatment. Lipopolysaccharide-elicited neutrophil recruitment was enhanced in the lungs of dexamethasone-treated calves compared to saline-treated controls. These findings indicate that modulation of epithelial antimicrobial peptide expression is one mechanism through which corticosteroids and stress may impair innate pulmonary defenses.

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Section: Discussionmentioning

confidence: 99%

Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells

et al. 2007

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“…Whereas in one study LPS-dependent hBD-2 induction in a human airway cell line can be inhibited by corticosteroids [129], another study failed to identify inhibitory effects of dexamethason upon hBD-2 induction in bronchial epithelial cells, but observed inhibition of hBD-3 induction [130]. In skin keratinocytes all-trans retinoic acid dose-dependently downregulated hBD-2, hBD-3 and hBD-4 induction by various stimuli, suggesting that these therapeutics may have yet unrecognised side effects by downregulating innate epithelial defense effector molecule expression [108].…”

Section: Downregulation Of B-defensin Expressionmentioning

confidence: 99%

Antimicrobial skin peptides and proteins

Schröder

Harder

2006

Cell. Mol. Life Sci.

222

216

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Human skin is permanently exposed to microorganisms, but rarely infected. One reason for this natural resistance might be the existence of a 'chemical barrier' consisting in constitutively and inducibly produced antimicrobial peptides and proteins (AMPs). Many of these AMPs can be induced in vitro by proinflammatory cytokines or bacteria. Apart from being expressed in vivo in inflammatory lesions, some AMPs are also focally expressed in skin in the absence of inflammation. This suggests that non-inflammatory stimuli of endogenous and/or exogenous origin can also stimulate AMP synthesis without inflammation. Such mediators might be ideal 'immune stimulants' to induce only the innate antimicrobial skin effector molecules without causing inflammation.

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“…In humans, the ␣-defensins are mainly expressed in neutrophils (human neutrophil peptides 1-4) and intestinal Paneth epithelial cells (human defensins 5 and 6) (9, 10). In contrast, hBDs, four of which (hBD-1 to -4) have been identified and characterized to date, are largely expressed in various epithelial tissues, including lung and skin (7,(13)(14)(15)(16)(17)(18)(19)(20). Interestingly, hBD-2 to -4 are highly inducible, whereas expression of hBD-1 is constitutive (7,11,19).…”

Section: Modulation Of Humanmentioning

confidence: 99%

Modulation of Human β-Defensin-2 Transcription in Pulmonary Epithelial Cells by Lipopolysaccharide-Stimulated Mononuclear Phagocytes Via Proinflammatory Cytokine Production

Tsutsumi‐Ishii

Nagaoka

2003

The Journal of Immunology

157

150

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Human β-defensin (hBD)-2, a cationic antimicrobial peptide primarily induced in epithelial cells in response to inflammatory stimuli, plays an important role in host defense. To elucidate the expression mechanism of hBD-2 in the lung, we investigated the modulation of hBD-2 transcription in pulmonary epithelial cells by mononuclear phagocytes stimulated with LPS. Coculture of A549 pulmonary epithelial cells with Mono-Mac-6 monocytic cells in the presence of Escherichia coli LPS markedly up-regulated hBD-2 promoter activity, whereas A549 alone did not respond to LPS to activate the hBD-2 promoter. Furthermore, IL-1β and TNF-α in the culture supernatants from LPS-stimulated monocytic cells activated the hBD-2 promoter in A549 cells. Of note, IL-1β was more potent than TNF-α in this effect. In addition, a mutation of the NF-κB site at −200 (pκB1 site) completely abolished this IL-1β- and TNF-α-induced hBD-2 promoter activation, whereas NF-κB inhibitors (MG-132 and helenalin) strongly suppressed it. Moreover, electrophoretic mobility shift assay suggested that NF-κB, consisting of p65-p50 heterodimer, could bind to the pκB1 site in cytokine-stimulated A549 cells. Interestingly, flow cytometric analysis revealed that A549 cells expressed CD14 but lacked Toll-like receptor 4, which may account for the hyporesponsiveness of A549 cells to LPS. Taken together, these results suggest that hBD-2 expression in pulmonary epithelial cells is modulated by NF-κB via the actions of IL-1β and TNF-α produced by LPS-stimulated mononuclear phagocytes.

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Inhibition of hBD-3, but Not hBD-1 and hBD-2, mRNA Expression by Corticosteroids

Cited by 54 publications

References 24 publications

Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells

Effect of Corticosteroids and Neuropeptides on the Expression of Defensins in Bovine Tracheal Epithelial Cells

Antimicrobial skin peptides and proteins

Modulation of Human β-Defensin-2 Transcription in Pulmonary Epithelial Cells by Lipopolysaccharide-Stimulated Mononuclear Phagocytes Via Proinflammatory Cytokine Production

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