Identification and functional importance of IL-1 receptors on rat parietal cells

Abstract

We studied the expression of interleukin-1 (IL-1) receptors and the effect of IL-1β on the function of highly enriched (>97%) rat parietal cells. RT-PCR of parietal cell poly(A)+RNA with primers specific for the rat IL-1 receptor revealed a single 547-kb PCR product highly homologous to the published sequence of the IL-1 receptor. Northern blot analysis of poly(A)+RNA of rat parietal cells and brain revealed a single RNA species of 5.7 kb. Cytochemistry of parietal cell IL-1 receptor was performed with biotinylated recombinant human IL-1β, visualized by avidin-coupled fluorescein. Corresponding to the high degree of parietal cell enrichment, 95% of the cells stained positive. Basal H+production ([14C]aminopyrine accumulation) was not changed by IL-1β (0.25–100 pg/ml) nor was the response to histamine or carbachol when added simultaneously with the cytokine. However, when parietal cells were preincubated with IL-1β (0.5–5 pg/ml) for 10 min before the addition of histamine or carbachol, the response to these secretagogues was reduced by 35 and 67%, respectively. Inhibition by IL-1β was fully reversed by the human recombinant IL-1 receptor antagonist. Preincubation of parietal cells with IL-1β failed to alter histamine-stimulated cAMP production but markedly inhibited carbachol-induced formation ofd- myo-inositol 1,4,5-trisphosphate. In fura 2-loaded, purified parietal cells, 10 min preincubation with IL-1β dramatically reduced the initial transient peak elevation of intracellular Ca2+concentration in response to carbachol. We conclude that rat parietal cells express IL-1 receptors mediating inhibition of H+production. The antisecretory effect of IL-1β may contribute to hypoacidity secondary to acute Helicobacter pylori infection or during chronic colonization by H. pylori preferring the fundic mucosa.

Prostacyclin signaling regulates circulating ghrelin during acute inflammation

“…In contrast, we demonstrated robust expression of IL-1R1 mRNA and protein in the gastric mucosa, primarily distributed at the base of the gastric mucosa, and extending to a limited extent toward the luminal surface. These data are consistent with previously published reports of IL-1R1 expression in freshly isolated rat parietal cells as well as in gastric carcinoma cell lines (Beales & Calam 1998, Schepp et al 1998, Beales 2002. Although the tissue distribution of IL-1R1 matches the distribution of ghrelin-producing cells, we found no evidence of colocalization of ghrelin with the IL-1R1, indicating that the effect of IL-1b on ghrelin secretion is due to the paracrine action of a second messenger.…”

Expression of Intrinsic Factor in Rat and Murine Gastric Mucosal Cell Lineages Is Modified by Inflammation

“…9,10 Moreover, IL-1 receptors are found on the surface of parietal cells. 11 Therefore, models of chronic inflammation of the zymogenic mucosa were selected to test whether increased elaboration of cytokines could enlarge the population of parietal cells that produce IF.…”

The role of Sp1 in IL-1β andH. pylori-mediated regulation of H,K-ATPase gene transcription

“…Our recent report of IL-1␤ activation, and not inhibition, of human HK␣ promoter-Luc reporter constructs transfected into AGS cells (24) suggests that IL-1␤ inhibits acid secretion at a posttranslational rather than transcriptional level. As a potent inhibitor of gastric acid secretion, IL-1␤ probably contributes to H. pylori-induced hypochlorhydria through impairment of inositol (1,4,5)-triphosphate-dependent increase in intracellular Ca 2ϩ concentration (26) and consequent failure of parietal cell tubulovesicular fusion and H,K-ATPase activation. Evidence that H. pylori interferes with the normal regulation of HK␣ transcription has accrued from studies examining the effects of H. pylori in the HK␣ promoter-transfected AGS cell model (13,25), and we have recently reported that the mechanistic basis of HK␣ downregulation by H. pylori is ERK1/2-mediated NF-B p50 homodimer binding to an NF-B 1 cis-response element at Ϫ170 to Ϫ150 bp on the HK␣ 5Ј-flanking sequence (25).…”