Abstract
BackgroundProgressive airway inflammation and susceptibility to the airway colonisation and infection are characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). Antimicrobial peptides (AMPs) are central to the function of the innate host immune response against microbial pathogens and are regulators of inflammation and immunity. S100A7/psoriasin, a recently described AMP, is an essential component of the human epithelia against invading pathogens and acts as an effector molecule of the host innate defence in the skin. We hypothesized that S100A7/psoriasin is involved in the airway mucosal immunity and differently regulated and expressed in the lung during progression of COPD.MethodsS100A7/psoriasin gene expression was assessed in bronchial biopsies and bronchoalveolar lavage (BAL) fluid cells of healthy controls and COPD patients. Using confocal microscopy and immunohistochemistry, the protein expression of S100A7/psoriasin was investigated.ResultsHere, we report that S100A7/psoriasin, the major antimicrobial peptide of the human skin, is constitutively expressed in perinuclear granules of human bronchial epithelial cells and alveolar macrophages. Whereas typical activators of the innate immune response like TLR ligands and cytokines induced the upregulation of CXCL-8 mRNA and release of CXCL-8 by epithelial cells, S100A7/psoriasin mRNA expression was not modulated. To investigate a potential association of S100A7/psoriasin with COPD, S100A7/psoriasin mRNA expression was assessed in bronchial biopsies and BAL fluid cells of patients at different stages of COPD and controls. Overall, 10 healthy individuals and 34 COPD patients were enrolled in this study. We found an association of S100A7/psoriasin mRNA expression with bacterial detection in the tracheobronchial system (p = 0.0304), which was the strongest in individuals positive for with S. aureus (p = 0.0005). However, S100A7/psoriasin mRNA expression was not altered during the progression of COPD.ConclusionsS100A7/psoriasin gene expression is unchanged in the airways during COPD. The newly identified association of S100A7/psoriasin with S. aureus may provide new insights into the antimicrobial defence response of the human airways, leading to the induction of S100A7/psoriasin upon microbial challenge.
Highlights
Progressive airway inflammation and susceptibility to the airway colonisation and infection are characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD)
We first tried to identify the expression of S100A7/psoriasin mRNA in the human bronchial and lung epithelial cell lines NCI-H727 and A549, respectively
To further analyze whether lung epithelial cells could be stimulated for the induction of an enhanced S100A7/psoriasin expression, we treated the cells with the TLR4 ligand LPS, as well as with the proinflammatory cytokines IL-1b and TNF-a but found that S100A7/psoriasin mRNA expression remained unchanged over at least 20 hours, regardless of the type of stimuli used (Figure 2, right panels)
Summary
Progressive airway inflammation and susceptibility to the airway colonisation and infection are characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). As the inhaled air is not sterile, respiratory cells are cytokines, chemotactic factors as well as a variety of antimicrobial substances [4,5]. Among these substances are C-type lectins such as SP-A and SP-D [6], LL37/ CAP-18 [7], SLPI [8], and antimicrobial peptides such as b-defensins [9,10,11,12]. The role of antimicrobial peptides (AMPs) in the innate immune defense mechanisms of human airways and lungs has recently gained more clinical interest [13]. Among a group of recently described antimicrobial peptides that are produced by human epithelial cells, S100A7/psoriasin exhibits very strong antimicrobial activity at low molecular concentrations [14], which was confirmed by comparing the activity of natural Nacetylated S100A7/psoriasin with that of chemically synthesized N-acetylated S100A7 [15]
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