Adrenomedullin expression by gastric epithelial cells in response to infection.

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 beta-defensins. Upon exposure of human gastric epithelial cells to viable cells of invasive or noninvasive strains of Helicobacter pylori, Escherichia coli, Salmonella enterica, or Streptococcus 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 1 alpha (IL-1 alpha), 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 to E. coli or Mycobacterium 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.