Pulmonary Macrophages Can Stimulate Cell Growth of Bovine Bronchial Epithelial Cells

Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor-γ (PPARγ) ligands that are widely used in type II diabetes treatment. In addition to their ability to improve glucose homeostasis, TZDs possess anti-inflammatory properties and inhibit growth of many cells, particularly cancerous airway epithelial cells. However, the functional effects of PPARγ ligands on nonmalignant human bronchial epithelial cells have never been investigated. In the present study, we questioned whether PPARγ ligands may regulate proliferation of human bronchial epithelial cells, and we studied their potential molecular mechanisms. We found that synthetic PPARγ agonists, rosiglitazone (RGZ) and troglitazone (TGZ), induced proliferation of human bronchial epithelial cells, whereas the endogenous PPARγ ligand, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), inhibited cell growth. RGZ and TGZ (10 μM) induced a rapid and transient intracellular Ca2+ mobilization from thapsigargin-sensitive intracellular stores, whereas 15d-PGJ2 (5 μM) did not induce any Ca2+ signal. The PPARγ antagonist GW-9662 did not inhibit any biological responses, but it reversed the effect of 15d-PGJ2 on cell growth. Using RT-PCR, we detected mRNA expression of the GPR40 receptor, a G protein-coupled 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 Ca2+ 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 Ca2+ signaling pathway.

Download Full-text

Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(91)90414-j ◽

1991 ◽

Vol 87 (5) ◽

pp. 930-938 ◽

Cited By ~ 27

Author(s):

Maurizio Mezzetti ◽

Massimo Soloperto ◽

Angelo Fasoli ◽

Sabrina Mattoli

Keyword(s):

T Cells ◽

Epithelial Cells ◽

Dna Synthesis ◽

Antigen Presenting Cells ◽

Bronchial Epithelial Cells ◽

Human Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Pulmonary Macrophages ◽

Antigen Presenting

Download Full-text

Clarithromycin Delays Progression of Bronchial Epithelial Cells from G1 Phase to S Phase and Delays Cell Growth via Extracellular Signal-Regulated Protein Kinase Suppression

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.50.5.1738-1744.2006 ◽

2006 ◽

Vol 50 (5) ◽

pp. 1738-1744 ◽

Cited By ~ 24

Author(s):

Masaharu Shinkai ◽

Jun Tamaoki ◽

Hideo Kobayashi ◽

Soichiro Kanoh ◽

Kazuo Motoyoshi ◽

...

Keyword(s):

Cell Growth ◽

Epithelial Cells ◽

Bronchial Epithelial Cells ◽

S Phase ◽

Macrolide Antibiotics ◽

Quiescent State ◽

Bronchial Epithelial ◽

Extracellular Signal ◽

M Phase ◽

Normal Human

ABSTRACT The nonsteroidal anti-inflammatory drugs have been shown to support cytoprotection of cells by shifting cells toward a quiescent state (G0/G1). Extracellular signal-regulated kinase (ERK) is required for cells to pass from G1 phase into S phase, and macrolide antibiotics can inhibit ERK1/2 phosphorylation. However, previous reports suggest that macrolide antibiotics do not affect cell growth in bronchial epithelial cells. Therefore, we studied normal human bronchial epithelial (NHBE) cells to determine whether clarithromycin (CAM) suppresses ERK, delays bronchial epithelial cells from progressing to S phase, and delays cell growth. Exposure to CAM at 10 μg/ml daily over 4 days irreversibly decreased the cell proliferation with and without growth supplements (P < 0.0001). CAM also inhibited ERK1/2 phosphorylation over the first 90 min of exposure (P < 0.05 for 30 min, P < 0.0001 for 60 min, and P < 0.01 for 90 min) and decreased the ratio of phosphorylated ERK1/2 (pERK1/2) to total ERK1/2 (tERK1/2) (P < 0.0001). Incubation with CAM for 48 h increased the proportion of cells in G1 phase (means ± standard deviations) from 63.5% ± 0.9% to 79.1% ± 1.4% (P < 0.0001), decreased that in S phase from 19.8% ± 1.2% to 10.0% ± 2.1% (P < 0.01), and decreased that in G2/M phase from 16.7% ± 0.4% to 11.0% ± 0.8% (P < 0.001). In contrast, the ratio of pMEK1/2 to tMEK1/2 was not altered after exposure to CAM. These results suggest that macrolide antibiotics can delay the progression of NHBE cells from G1 phase to S phase and can slow cell growth, probably through the suppression of ERK1/2.

Download Full-text