Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins.

  title={Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins.},
  author={Sandra van Wetering and Abraham C. Van Der Linden and M A van Sterkenburg and Willem I. de Boer and Astrid L. A. Kuijpers and Joost Schalkwijk and Pieter S. Hiemstra},
  journal={American journal of physiology. Lung cellular and molecular physiology},
  volume={278 1},
Secretory leukocyte proteinase inhibitor (SLPI) is a serine proteinase inhibitor that is produced locally in the lung by cells of the submucosal bronchial glands and by nonciliated epithelial cells. Its main function appears to be the inhibition of neutrophil elastase (NE). Recently, NE was found to enhance SLPI mRNA levels while decreasing SLPI protein release in airway epithelial cells. Furthermore, glucocorticoids were shown to increase both constitutive and NE-induced SLPI mRNA levels. In… 

Figures and Tables from this paper

Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity.

  • J. Sallenave
  • Biology
    American journal of respiratory cell and molecular biology
  • 2010
Data emanating from patients with chronic pathologies have shown that SLPI and elafin are often inactivated in inflammatory secretions, either through the action of host or microbial products, justifying attempts at antiprotease supplementation in clinical protocols.

Human mast cells decrease SLPI levels in type II – like alveolar cell model, in vitro

The results indicate that SLPI-producing cells may assist mast cell migration and that the regulation of SLPI release and/or consumption by mast cells requires interaction between these cell types.

Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone

The results from the present study indicate that defensins differentially induce cytokine secretion by A549 cells and primary bronchial epithelial cells, whereas in PBEC only IL-8 and IL-6 were increased.

SLPI and elafin: one glove, many fingers.

It is believed that elafin and SLPI are important molecules in the controlled functioning of the innate immune system, and may have further importance in the integration of this system with the adaptive immune response.

Elafin, an Elastase-specific Inhibitor, Is Cleaved by Its Cognate Enzyme Neutrophil Elastase in Sputum from Individuals with Cystic Fibrosis*

Evidence is provided that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect, which may have repercussions on the innate immune function of elAFin.

Differential effects of periopathogens on host protease inhibitors SLPI, elafin, SCCA1, and SCCA2

The results suggest that different periopathogens affect the host protease inhibitors in a different manner, suggesting host susceptibility may differ in the presence of these pathogens.

Antimicrobial Peptides SLPI and Beta Defensin-1 in Sputum are Negatively Correlated with FEV1

Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function and ICS use was associated with higher sputum osteopontin compared to those with no ICSUse.

Human neutrophil defensins induce lung epithelial cell proliferation in vitro

Data suggest that neutrophil defensins may possibly be involved in epithelial repair in the airways by inducing lung epithelial cell proliferation through an EGF receptor‐independent, MAP kinase signaling pathway.

SLPI and inflammatory lung disease in females.

How SLPI participates in these events and speculate on whether regulatory mechanisms such as post-transcriptional modulation by miRNAs (microRNAs) are important in the control of SLPI expression in inflammatory lung disease.



Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester.

SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels.

Secretion of mucus proteinase inhibitor and elafin by Clara cell and type II pneumocyte cell lines.

It is shown for the first time that MPI and elafin (and its precursor) are secreted by the A549 cell line, which implicates the type II alveolar cell in the defense of the peripheral lung against the neutrophil elastase secreted during inflammation.

Effect of defensins on interleukin-8 synthesis in airway epithelial cells.

The findings suggest that defensins, released by stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and thus may mediate the recruitment of additional neutrophil into the airways.

Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes.

Alveolar epithelial cells may respond to cytokines secreted during the onset of inflammation by increasing their antiprotease shield and elafin/pre-elafin seems to be a true local "acute phase reactant" whereas SLPI, in comparison, may be less responsive to local inflammatory mediators.

Corticosteroids increase secretory leukocyte protease inhibitor transcript levels in airway epithelial cells.

The interaction between elastase and fluticasone is examined and it is found they act synergistically to increase SLPI transcript levels, suggesting that corticosteroids may exert their antiinflammatory effects in part by increasing airway epithelial cell SLPI production.

Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung.

Elafin is a constituent of BAL fluid from normal subjects and is found in enhanced concentrations in FL and in farmers with lymphocytic alveolitis, suggesting that elafin may play a role in lung homeostasis and inflammation.

Pseudomonas aeruginosa lipopolysaccharide induces CF-like alteration of protein secretion by human tracheal gland cells.

It is shown that LPS downregulated cystic fibrosis transmembrane conductance regulator (CFTR) mRNA expression in HTG cells indicative of a link between CFTR function and consequent CF-like alteration in protein secretory process.

Neutrophil elastase increases secretory leukocyte protease inhibitor transcript levels in airway epithelial cells.

It is found that neutrophil elastase increased SLPI transcript levels in primary and transformed human airway epithelial cells in a time- and dose-dependent manner, demonstrating one way in which secretory leukocyte protease inhibitor is regulated, via a protease that it inhibits.

Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia.

It is shown that SKALP is constitutively expressed in several epithelia that are continuously subjected to inflammatory stimuli, such as the oral cavity and the vagina where it co-localizes with type 1 TGase, which strongly suggest that the constitutive expression ofSKALP in squamous epithelian, and the inducible expression in epidermis participate in the control of epithelial integrity, by inhibiting PMN derived proteinases.

Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E2, and matrix metalloproteinases.

It is demonstrated that SLPI also functions as a potent antiinflammatory agent by interfering with the signal transduction pathway leading to monocyte MMP production.