Effect of glucocorticoids on the synthesis of antimicrobial peptides in amphibian skin

Simmaco, Maurizio; Boman, Anita; Mangoni, Maria Luisa; Mignogna, Giuseppina; Miele, Rossella; Barra, Donatella; Boman, Hans G.

doi:10.1016/s0014-5793(97)01216-7

Cited by 66 publications

(75 citation statements)

References 27 publications

(35 reference statements)

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“…Our in vivo observations are consistent with a study on human fetal lung explants, which demonstrated that hBD-2 mRNA expression was reduced by dexamethasone treatment, while expression of hBD-1 mRNA was increased (45). Similarly, frogs treated with corticosteroids had reduced expression of antimicrobial peptides and failed to reduce the number of bacteria in an experimental oral infection compared to untreated frogs (43,44). The reduction of antimicrobial peptide expression by glucocorticoids seems counterintuitive, as circumstances that elevate endogenous glucocorticoids, such as stress or infection, would likely benefit from the induction of epithelial antimicrobial activity.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

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

et al. 2007

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“…Activation of such transcription factors and binding to their consensus sequences have also been observed in fish (25,31,32). This suggests that the flounder may regulate pleurocidin gene expression in response to infection and inflammation, in a manner similar to that seen for antimicrobial peptide genes from amphibians (27,38), insects (11), and mammals (9).…”

Section: Discussionmentioning

confidence: 73%

Characterization of a Fish Antimicrobial Peptide: Gene Expression, Subcellular Localization, and Spectrum of Activity

Cole

Darouiche

Legarda

et al. 2000

Antimicrob Agents Chemother

142

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Antimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broadspectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from the skin secretions of winter flounder (Pleuronectes americanus). The present study identifies the cDNA and gene encoding pleurocidin. The pleurocidin gene comprises four exons. Its upstream region demonstrates consensus binding sequences for transcription factors found in host defense genes in mammals, including sequences identical to the NF-IL6 and alpha and gamma interferon response elements. Pleurocidin is predicted to exist as a 68-residue prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal and carboxy-terminal anionic propiece to form the active, mature peptide. Transmission electron microscopy localized pleurocidin to the mucin granules of skin and intestinal goblet cells. Significant synergy was shown to occur between pleurocidin and D-cycloserine targeting Mycobacterium smegmatis. Pleurocidin was functionally active at physiologic concentrations of magnesium and calcium; however, high concentrations of these divalent cations ablated pleurocidin's activity against a standard test strain, Escherichia coli D31. Pleurocidin was tested against bacterial and fungal clinical isolates and showed broad-spectrum antimicrobial activity. Together, these data support the hypothesis that pleurocidin participates in innate mucosal immunity, and it may prove to be a beneficial therapeutic agent.Increasing evidence suggests that endogenous peptides with antimicrobial properties play an important role in host defense. These peptides possess marked microbicidal activity and have been isolated from a variety of cells of myeloid lineage and mucosal surfaces in most species tested thus far (4,5,8,12). The recent focus has been on mucus-derived peptides and their roles in innate host defense at organism-environment interfaces, such as the integument and the respiratory and digestive epithelia. The multitude of peptides discovered at mucosal surfaces include human ␤-defensin 1 (HBD-1) in urogenital tissues (43) and bronchoalveolar lavage fluid (39), HBD-2 at sites of inflammation (24, 39), cryptdins from the Paneth cells (18), tracheal antimicrobial peptide (TAP) and lingual antimicrobial peptide (LAP) from cows (10, 33), and magainin and PGLa from frogs (46). Each peptide class confers a broad spectrum of antimicrobial activity and cationic charge at physiologic pH. Many peptides show high interspecies cDNA and protein sequence homology, frequently across evolutionarily diverse phyla.We recently discovered pleurocidin, a novel 25-residue linear antimicrobial peptide in the skin mucous secretions of the winter flounder, Pleuronectes americanus (6). The sequence of the mature molecule, GWGSFFKKAAHVGKHVGKAAL THYL, shows sequence homology with the dermaseptin (tree frog) and ceratotoxin (medfly) classes of antimicrobial peptides. Pleurocidin is a highly basic...

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“…Moreover, we showed that treatment of frogs with glucocorticoids results in the up-regulation of IkBa and almost complete inhibition of the de novo synthesis of antimicrobial peptides in skin secretions [13,14].…”

mentioning

confidence: 91%

Involvement of Rel factors in the expression of antimicrobial peptide genes in amphibia

Miele¹,

Bjorklund²,

Barra³

et al. 2001

Eur J Biochem

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Genes coding for antimicrobial peptides in amphibia reveal a remarkably high number of structural motifs for response elements, previously identified in the genes of insect antimicrobial peptides and in those of the mammalian acute phase response. This study focuses on the functional analysis of the bombinin gene promoter in a Drosophila blood cell line, and the identification of kB-binding factors in skin secretions of the frog Bombina orientalis. Transfection experiments demonstrated that the bombinin gene promoter was activated in a lipopolysaccharidedependent manner, and that insect Rel factors target specific sequences in the amphibian gene promoter. After bathing frogs in bacteria, their skin secretions contained kB-specific binding complexes, indicating that Rel factors are crucial components in the response against gramnegative bacteria in this species. These results suggest that a common ancestral control mechanism governs the expression of the first line host-defence from insects to vertebrates.

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Effect of glucocorticoids on the synthesis of antimicrobial peptides in amphibian skin

Cited by 66 publications

References 27 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

Characterization of a Fish Antimicrobial Peptide: Gene Expression, Subcellular Localization, and Spectrum of Activity

Involvement of Rel factors in the expression of antimicrobial peptide genes in amphibia

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