Adrenomedullin Expression by Gastric Epithelial Cells in Response to Infection

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Abstract
Many surface epithelial cells express adrenomedullin, a multifunctional peptide found in a wide number of body and cell systems. Recently, we and others have proposed that adrenomedullin has an important novel role in host defense. This peptide has many properties in common with other cationic antimicrobial peptides, including the human β-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains ofHelicobacter pylori,Escherichia coli,Salmonella enterica, orStreptococcus bovis, a significant increase in adrenomedullin secretion from these cells was demonstrated. Adrenomedullin gene expression was also increased in response to these microorganisms. Similar observations were noted when these cells were incubated with proinflammatory cytokines such as interleukin 1α (IL-1α), IL-6, tumor necrosis factor alpha and lipopolysaccharide. In cultured cells and an animal infection model, increased adrenomedullin peptide and gene expression was demonstrated when exposed toE. coliorMycobacterium paratuberculosis, respectively. The data suggest there is a strong association between epithelial infection, inflammation, and adrenomedullin expression, which may have clinical relevance. The regulation of adrenomedullin expression may have therapeutic applications, such as improving or enhancing mucosal immunity.

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