scholarly journals Immunomodulatory Effect of Linezolid on Methicillin-Resistant Staphylococcus aureus Supernatant-Induced MUC5AC Overexpression in Human Airway Epithelial Cells

2014 ◽  
Vol 58 (7) ◽  
pp. 4131-4137 ◽  
Author(s):  
Norihito Kaku ◽  
Katsunori Yanagihara ◽  
Yoshitomo Morinaga ◽  
Koichi Yamada ◽  
Yosuke Harada ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Protein Production ◽  
Airway Epithelial Cells ◽  
Protein Kinase Inhibitors ◽  
Immunomodulatory Effect ◽  
Airway Epithelial ◽  
Major Barrier ◽  
Methicillin Resistant

ABSTRACTLinezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methicillin-resistantStaphylococcus aureus(MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the effect of linezolid on MRSA-induced MUC5AC overexpression in airway epithelial cells. In this study, an MRSA supernatant was used to avoid the direct effect of linezolid on MRSA. MUC5AC protein production was significantly increased with a 40-fold dilution of MRSA supernatant. At the mRNA level, MUC5AC gene expression was significantly increased 6 and 9 h after stimulation. In an inhibition study, linezolid significantly reduced MRSA-induced MUC5AC protein and mRNA overexpression at concentrations of 5 and 20 μg/ml, which were the same as the trough and peak concentrations in human epithelial lining fluid. In an analysis of cell signaling, among the mitogen-activated protein kinase inhibitors, only the extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor reduced the MUC5AC protein production to the same level as that of the control; on Western blot analysis, only ERK1/2 was phosphorylated by the MRSA supernatant. In addition, the ERK1/2 phosphorylation was inhibited by linezolid. MUC5AC and MUC5B are the major barrier that traps inhaled microbial organisms, particulates, and foreign irritants. However, in patients with chronic respiratory diseases, pathogen-induced MUC5AC overexpression causes many problems, and control of the overexpression is important. Thus, this study revealed that linezolid showed a direct immunomodulatory effect in airway epithelial cells.

Kappa‐carrageenan sinus rinses reduce inflammation and intracellular Staphylococcus aureus infection in airway epithelial cells

2019 ◽  
Vol 9 (8) ◽  
pp. 918-925 ◽  
Author(s):  
Catherine Bennett ◽  
Mahnaz Ramezanpour ◽  
Clare Cooksley ◽  
Sarah Vreugde ◽  
Alkis James Psaltis
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Aureus Infection ◽  
Kappa Carrageenan

scholarly journals The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 360
Author(s):  
Janina Treffon ◽  
Sarah Ann Fotiadis ◽  
Sarah van Alen ◽  
Karsten Becker ◽  
Barbara C. Kahl
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Airway Epithelial Cells ◽  
Farm Animals ◽  
Airway Epithelial ◽  
Methicillin Resistant ◽  
Virulence Potential ◽  
Airway Infections ◽  
Severe Infections

Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A

2008 ◽  
Vol 294 (6) ◽  
pp. L1187-L1196 ◽  
Author(s):  
Rong Ji ◽  
Clement M. Lee ◽  
Linda W. Gonzales ◽  
Yi Yang ◽  
Mark O. Aksoy ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Splice Variant ◽  
Cell Movement ◽  
Airway Epithelial Cells ◽  
Type Ii Cells ◽  
Type Ii ◽  
Airway Epithelial ◽  
Transfected Cells ◽  
Type Ii Pneumocytes

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca2+ and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca2+ activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

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