Bacterial infection of osteoblasts induces interleukin-1beta and interleukin-18 transcription but not protein synthesis.
A growing body of evidence has shown that bacterially challenged bone-forming osteoblasts are a significant source of an array of cytokines and chemokines that can support immune responses during bone disease. In the present study, Staphylococcus aureus and Salmonella, two common pathogens of bone, were investigated for their ability to induce production of two related inflammatory cytokines, interleukin-1beta (IL-1beta) and IL18, in osteoblasts. Cultured mouse osteoblasts were found to respond rapidly to either bacterial challenge by upregulation in the levels of mRNA encoding both IL-1beta and IL-18. Surprisingly, this mRNA expression did not translate into intracellular accumulation of IL-1beta or IL-18 precursor proteins or secretion of mature cytokines, despite the presence of detectable caspase-1 activity in these cells. These studies demonstrate that although osteoblasts can secrete a number of key proinflammatory mediators in response to bacterial pathogens, IL-1beta and IL-18 are not among this number. We suggest that osteoblasts are an unlikely source of these cytokines during the progression of bacterial infection of bone.
Marriott
Ian
I
Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA. imarriot@email.uncc.edu
Hughes
Francis M
FM
Bost
Kenneth L
KL
D000818:Animals; D000831:Animals, Newborn; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D007375:Interleukin-1 / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000096:biosynthesis*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000276:immunology* / Q000382:microbiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012475:Salmonella / Q000502:physiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D007375:Interleukin-1; D020382:Interleukin-18; D012333:RNA, Messenger; D020169:Caspases