IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion.
Previously, we reported that epithelial cells respond to exogenous interleukin (IL)-1α by increasing expression of several genes involved in the host response to microbes, including the antimicrobial protein complex calprotectin (S100A8/A9). Given that S100A8/A9 protects epithelial cells against invading bacteria, we studied whether IL-1α augments S100A8/A9-dependent resistance to bacterial invasion of oral keratinocytes. When inoculated with Listeria monocytogenes, human buccal epithelial (TR146) cells expressed and released IL-1α. Subsequently, IL-1α-containing media from Listeria-infected cells increased S100A8/A9 gene expression in naïve TR146 cells an IL-1 receptor (IL-1R)-dependent manner. Incubation with exogenous IL-1α decreased Listeria invasion into TR146 cells, whereas invasion increased with IL-1R antagonist. Conversely, when S100A8/A9 genes were knocked down using short hairpin RNA (shRNA), TR146 cells responded to exogenous IL-1α with increased intracellular bacteria. These data strongly suggest that infected epithelial cells release IL-1α to signal neighboring keratinocytes in a paracrine manner, promoting S100A8/A9-dependent resistance to invasive L. monocytogenes.
Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, USA.
B S
BS
Sorenson
A
A
Khammanivong
B D
BD
Guenther
K F
KF
Ross
M C
MC
Herzberg
D040501:Calgranulin A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040502:Calgranulin B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D053582:Interleukin-1alpha / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008089:Listeria monocytogenes / Q000276:immunology* / Q000472:pathogenicity; D008088:Listeriosis / Q000188:drug therapy / Q000276:immunology*; D009061:Mouth Mucosa / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000187:drug effects
D040501:Calgranulin A; D040502:Calgranulin B; D017077:Culture Media, Conditioned; D053582:Interleukin-1alpha; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1