Expression of the Cyclooxygenase-2 Gene in Gastric Epithelium

Abstract

This study examined the mRNA level of cyclooxygenase-2 (cox-2) in a rat gastric mucosal cell line after growth stimulation in vitro and in rat gastric mucosa before and after acid-induced injury in vivo. RGMI cells were stimulated with fetal calf serum in the in vitro study. Thereafter, the cox-2 mRNA level was examined by Northern analysis. Effects of NS-398, a specific inhibitor of cox-2, and indomethacin on prostaglandin production and cell proliferation were examined in RGM1 cells. In the in vivo study, rats were given 1 ml of 0.6 N hydrochloric acid into the stomach. The level of cox-2 mRNA was examined in rat gastric mucosa after acid administration. Cox-2 mRNA increased 20-60 min after growth stimulation in RGM1 cells. Both NS-398 and indomethacin suppressed prostaglandin production and cell proliferation after growth stimulation. Expression of cox-2 mRNA was observed 40 and 60 min after administration of 0.6 N HCl. Gastric lesions developed within 60 min after HCl administration and healed significantly within 48 h. The present study shows the expression of cox-2 in gastric epithelial cells in vitro and in gastric mucosa after injury in vivo. The results also suggest that cox-2 is involved in de novo synthesis of prostaglandins and cell proliferation in gastric epithelium.

Lansoprazole Induces Mucosal Protection through Gastrin Receptor-Dependent Up-Regulation of Cyclooxygenase-2 in Rats

“…An initial study by Seibert et al (1997) suggested that COX-1 mRNA was readily detectable in all normal tissue examined, especially in stomach and others, but that levels of COX-2 mRNA were substantially lower, with the exception of the brain. Several studies, including the present study, have shown that unstimulated gastric mucosa express a lower level of COX-2, whereas gastric mucosal epithelium expresses this isoform after various stimuli (Sawaoka et al, 1997;Sun et al, 2000). In the present study, lansoprazole enhanced the expression of mitogen-inducible COX-2, but not that of constitutive COX-1 in rat gastric mucosa.…”

“…The mitogen-inducible isoform (COX-2) is minimally expressed in normal stomach Kargman et al, 1996). COX-2 expression is enhanced, however, in gastric epithelial cells after growth stimulation in vitro and in gastric epithelium after acid-induced damage in vivo Sawaoka et al, 1997). We recently demonstrated that COX-2 protein is overexpressed during the healing of gastric lesions and a COX-2-specific inhibitor delays healing in the rat, suggesting an important role for this isozyme in gastric ulcer healing (Sun et al, 2000).…”

Constituents and Antiulcer Effect of Alchornea glandulosa: Activation of Cell Proliferation in Gastric Mucosa during the Healing Process

“…41) Hydrochloric acid is a necrotic agent that induces wide hemorrhagic bands in the gastric corpus 60 min after HCl administration. 42) Pretreatment with AG 50 min before HCl/ethanol solution increased the severity of lesions in a dose-dependent manner by 64% (250 mg/kg) and 46% (500 mg/kg), in relation to mice treated with vehicle (Table 3). We also observed that the lowest dose of AG showed the highest activity.…”

Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors

“…Although COX-2 expression in the healthy stomach is low and expression around a site of ulceration is considerably higher, it should be noted that rapid induction of COX-2 can occur, even in response to quite subtle mucosal irritation. A further functional role for COX-2 in mediating gastric epithelial proliferation has been demonstrated by Sawaoka et al (1997), whereas Nakatsugi et a1. (1996) have provided evidence that COX-2 contributes to mucosal defense in a rat model of stress ulcer.…”