Secretory phospholipase A2 is required to produce histologic changes associated with gastroduodenal reflux in a murine model

Abstract

The presence of secretory phospholipase A(2) appears necessary for early histologic changes produced by exposure of the esophagus to gastroduodenal contents. This enzyme is identified as a promising target for evaluation of mechanisms of carcinogenesis and chemoprevention of esophageal carcinoma.

The Secretory Phospholipase A2 Gene is Required for Gastroesophageal Reflux-Related Changes in Murine Esophagus

“…Though sPLA 2 induction in the setting of an inflammatory insult is not surprising, this is the first report of such in an animal reflux model. It is also consistent with previous reports of sPLA 2 overexpression in the setting of metaplastic change 11 and implies a sPLA 2 -dependent effect on esophageal mucosal proliferation in the setting of reflux.…”

“…10 We have observed in a murine model of gastroduodenal reflux that species of mice reported to be deficient in sPLA 2 do not manifest the usual histologic changes of hyperplasia and mucosal thickening in response to reflux. 11 In the present study, we demonstrate that the introduction of group IIa sPLA 2 into the naturally deficient C57BL/6 mouse restores its ability to generate mucosal hyperplasia in response to gastroduodenal reflux.…”

“…which naturally express sPLA 2 , had a robust hyperplastic response of the esophageal epithelium in response to gastroduodenal reflux. 11 This led us to hypothesize about a causative role for sPLA 2 in this model. Phospholipase A 2 refers to a group of enzymes which catalyze the rate-limiting step in the metabolism of phospholipids to produce arachidonic acid.…”

Circulating phospholipase-A2 activity in obstructive sleep apnea and recurrent tonsillitis

“…Several recent studies characterized the sPLA2 IIa expression level associated with oxidative stress [15], hyperplasia in response to inflammatory stimuli [18,19], malignant grade [12], and clinical features [13]. Our study revealed significant differences between the serum activity of sPLA2 IIa in the RT and OSA.…”

Gastroduodenal reflux induces group IIa secretory phospholipase A2expression and activity in murine esophagus

“…Balb/c mice, which naturally express group IIa sPLA 2 , develop histologic changes in the esophagus such as cell proliferation and mucosal thickening after 4 weeks of reflux. In contrast to this, C57BL/6 mice, which are naturally deficient in group IIa sPLA 2 secondary to a frameshift mutation in the gene, 13 are immune to these changes 14 …”