Hassan Lemjabbar

Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells

In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Gram-positive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein–coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin–binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4.

Viral dsRNA activates mucin transcription in airway epithelial cells

Double‐stranded (ds) RNA is a biologically active component of many viruses including rhinoviruses infecting the upper respiratory tract. Mucus production is a common symptom of such infections. Here, we show that mucin, the glycoprotein subunit of mucus gels, is transcriptionally upregulated in an NF‐κB‐ and p38‐dependent manner when homogeneous cultures of epithelial cells are exposed to dsRNA. Furthermore, upstream of p38 in this system, dsRNA stimulates the extracellular release of ATP and activation of cell surface ATP receptors, which are G protein‐coupled. This results in the stimulation of phospholipase C and protein kinase C. These findings suggest that ATP receptor antagonists could be used to modulate mucus production induced by virus.

Balance between MMP-9 and TIMP-1 expressed by human bronchial epithelial cells: relevance to asthma.

Human bronchial epithelial cells (HBECs) may play an important role in normal growth and development as well as in normal extracellular matrix turnover, thereby contributing in the maintenance of the structural and functional integrity of the lung. 1 HBECs may also be involved in responses to bronchial tree insults during inflammatory remodeling or wound healing. Injury to the bronchial epithelial surface, including mechanical trauma and toxin or inflammatory mediator exposure, 2 can result in sloughing of epithelial cells, leading to partial exposure of the basement membrane. The actual concept is that the wound repair process following epithelial denudation is achieved by a predictable sequence of resting epithelial cell spreading, migration, and proliferation. This process is probably affected by matrix metalloproteinases (MMPs) well known to degrade most matrix macromolecular components 3