Bacterially induced activation of interleukin-18 in porcine intestinal mucosa.
Interleukin (IL)-18 is a cytokine with structural and functional properties similar to IL-1beta and IL-12, respectively. It is activated by caspase-1 cleavage, like IL-1beta, and induces interferon (IFN)-gamma, like IL-12. In order to study the role of IL-18 in the immune response to infectious diseases of mucosal surfaces we cloned and expressed porcine IL-18 and developed antibodies to the protein. Porcine IL-18 retains the caspase-1 cleavage site present in other mammalian IL-18 proteins, but has two potential N-linked glycosylation sites not found in those proteins. Porcine interleukin-18 mRNA and protein are expressed in immune tissues including lymph nodes and gut associated lymphoid tissues. Specific cell types containing IL-18 include lung and splenic macrophages, nonadherent spleen cells and intestinal epithelial cells. Although IL-18 transcription is moderately induced by lipopolysaccharide, the magnitude and total expression level are small compared to those of interleukin-1beta. In vivo and ex vivo infection of intestinal mucosa with Salmonella choleraesuis resulted in a decrease in size of IL-18, consistent with cleavage of the preprotein by caspase-1. Thus, IL-18 is present in mucosal tissues where it could play a role in the immune response to invading pathogens.
Foss
D L
DL
Department of Veterinary PathoBiology, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA.
Zilliox
M J
MJ
Murtaugh
M P
MP
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D020382:Interleukin-18 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine / Q000378:metabolism*
D020382:Interleukin-18; D012333:RNA, Messenger