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Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor-[gamma] (PPAR[gamma]) ligands that are widely used in type II diabetes treatment. In addition to their ability to improve glucose homeostasis, TZDs possess antiinflammatory properties and inhibit growth of many cells, particularly cancerous airway epithelial cells. However, the functional effects of PPAR[gamma] ligands on nonmalignant human bronchial epithelial cells have never been investigated. In the present study, we questioned whether PPAR[gamma] ligands may regulate proliferation of human bronchial epithelial cells, and we studied their potential molecular mechanisms. We found that synthetic PPAR[gamma] agonists, rosiglitazone (RGZ) and troglitazone (TGZ), induced proliferation of human bronchial epithelial cells, whereas the endogenous PPAR[gamma], ligand, 15-deoxy-[[DELTA].sup.12,14]-prostaglandin [J.sub.2] (15d-[PGJ.sub.2]), inhibited cell growth. RGZ and TGZ (10 [micro]M) induced a rapid and transient intracellular [Ca.sup.2+] mobilization from thapsigargin-sensitive intracellular stores, whereas 15d-[PGJ.sub.2] (5 [micro]M) did not induce any [Ca.sup.2+] signal. The PPAR[gamma] antagonist GW-9662 did not inhibit any biological responses, but it reversed the effect of 15d-[PGJ.sub.2] on cell growth. Using RT-PCR, we detected mRNA expression of the GPR40 receptor, a G proteincoupled receptor recently identified as a receptor for free fatty acids and TZDs, in human bronchial epithelial cells. Downregulation of GPR40 by small-interfering RNA led to a significant inhibition of TZD-induced [Ca.sup.2+] mobilization and proliferation. This study provides evidence for the proliferative effect of anti-diabetic drug TZDs in nonmalignant human bronchial epithelial cells through GPR40 receptor activation, involving an intracellular [Ca.sup.2+] signaling pathway. airway epithelium; glitazone; calcium; peroxisome proliferator-activated receptor-[gamma]; G protein receptor 40

Staphylococcus aureus is a major cause of pulmonary infection, particularly in cystic fibrosis (CF) patients. However, few aspects of the interplay between S. aureus and host airway epithelial cells have been investigated thus far. We investigated by videomicroscopy the time- and bacterial concentration-dependent ([10.sup.4], [10.sup.6], and [10.sup.8] CFU/ml) effect of S. aureus on adherence, internalization, and the associated damage of the airway epithelial cells. The balance between the secretion by S. aureus of the [alpha]-toxin virulence factor and by the airway cells of the antibacterial secretory leukoproteinase inhibitor (SLPI) was also analyzed. After 1 h of interaction, whatever the initial bacterial concentration, a low percentage of S. aureus ( videomicroscopy; secretory leukoproteinase inhibitor; [alpha]-toxin; airway cell damage; bacterial adherence and internalization