LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells

Abstract

Our previous studies show that Bcl-2, a regulator of apoptosis, may be involved in the reduction of mucous cell metaplasia (MCM) during recovery from inflammatory responses. The present study was to determine whether neutrophilic inflammation mediates Bcl-2 expression in mucous cells. Rats were intratracheally instilled with 50–1,000 μg of LPS. The number of neutrophils recovered by bronchoalveolar lavage (BAL) increased with the dose of LPS, and the percentage of Bcl-2-expressing cells increased with the numbers of neutrophils in the BAL. Depletion of neutrophils did not reduce MCM, but the percentage of Bcl-2-positive cells increased 1.8-fold in neutrophil-depleted compared with controls. Injection of rats with bezafibrate, an inducer of cytochrome P-450, doubled the number of neutrophils in the BAL, decreased MCM twofold compared with vehicle-injected controls, and reduced Bcl-2 expression. Bcl-2 mRNA levels decreased in a tracheal epithelial cell line treated with bezafibrate. These data demonstrate that Bcl-2 expression is independent of the number of neutrophils in the BAL and that bezafibrate may directly reduce Bcl-2 expression in epithelial cells.

Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses?

“…Figure 6C suggests that Bcl-2-positive cells occurred only in animals in which the neutrophil count was Ͼ10 cells/l (equivalent to 20% neutrophils), and in RAO-affected animals, the number of Bcl-2-positive cells tended to increase with severity of neutrophilic inflammation. A similar association between the number of Bcl-2-positive mucous cells and numbers of neutrophils in airways also has been reported in rats challenged with two doses of endotoxin (6). However, neutrophils are not essential for Bcl-2 expression, because, in the latter model, neutrophil depletion did not reduce the number of Bcl-2-positive cells.…”

Resolution of LPS-induced airway inflammation and goblet cell hyperplasia is independent of IL-18

“…The onset of GCM correlates with the decline of PMN numbers as was shown in previous studies [12,6,15], and is maintained through d 6 when macrophage numbers are highest. We also observed that macrophage and PMN numbers were equal and lymphocyte numbers were maximum by d 4 when GCM is highest, suggesting that a combination of factors derived from these cell types, may be contributing to epithelial cell hyperplasia and increased mucin synthesis and storage resulting in GCM.…”

Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice

“…Notable, previous reports show that LPS exposure can upregulate Bcl-2 regardless of airway location and promote the differentiation of proliferating and preexisting epithelial cells into mucous cells [44,45] . Chronic LPS exposure may cause persistently elevated mucous cell numbers and contribute to mucous hypersecretion and airway obstruction as in chronic lung disease, such as cystic fibrosis or chronic bronchitis [44,45] .…”

“…Chronic LPS exposure may cause persistently elevated mucous cell numbers and contribute to mucous hypersecretion and airway obstruction as in chronic lung disease, such as cystic fibrosis or chronic bronchitis [44,45] . Although these previous reports and our present results appear to be contradictory, they are, in fact, two sides of the same coin.…”