A human oral keratinocyte cell line responds to human heat shock protein 60 through activation of ERK1/2 MAP kinases and up-regulation of IL-1β
| Autor: | John J. Taylor, Samantha J. Dainty, S Kapas, O Pleguezuelos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Keratinocytes
p38 mitogen-activated protein kinases medicine.medical_treatment Immunology Blotting Western Gingiva Proinflammatory cytokine Cell Line Basic Immunology Heat shock protein medicine Immunology and Allergy Humans Secretion RNA Messenger Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Reverse Transcriptase Polymerase Chain Reaction Chaperonin 60 Recombinant Proteins Up-Regulation Enzyme Activation medicine.anatomical_structure Cytokine Mitogen-activated protein kinase biology.protein HSP60 Keratinocyte Interleukin-1 Signal Transduction |
| Popis: | Summary Heat shock proteins (HSP) are released by cells in response to stress signals. It is hypothesized that pathogenic bacteria stimulate the cells in the periodontium to up-regulate the expression of HSP60, which would stimulate macrophages, and possibly other cells, to produce proinflammatory cytokines. We sought to determine whether oral keratinocytes responded to recombinant human HSP60 and to identify the signalling pathways involved. In addition, whether oral keratinocytes are a source of endogenous HSP60 was also investigated. RT-PCR revealed that rhHSP60 induced expression of the IL-1β gene in the Human Oral Keratinocyte (HOK-16B) cell line and it was highest at the lowest concentration used (0·1 µg/ml). These responses were mediated via activation of p44/42 MAP-kinases and to a lesser extend the MAP-kinase SAP/JNK. Similar data was obtained from analysis of intracellular signalling pathways in HOK-16B cells by rhHSP70 and LPS (from both E. coli and the oral pathogen Porphyromonas gingivalis). However, there was little activation of p38 by rhHSP60. Blocking of the p44/42 pathway decreased HSP60-induced IL-1β gene expression and protein secretion. In addition, we discovered that self-HSP60 proteins were constitutively secreted by HOK-16B cells. Secretion of self-HSP60 was up-regulated in cells treated with LPS from P. gingivalis, but down-regulated with LPS from E. coli. To summarize, oral keratinocytes respond to exogenous HSP60 by triggering expression of the inflammatory cytokine IL-1β through activation of p44/42 MAP kinase. Oral keratinocytes are also a source for self-HSP60 and the secretion of this protein may be differentially modified by LPS from different bacterial species. These results highlight the importance of oral keratinocytes and HSPs in the development of an immune response against bacterial infection. |
| Databáze: | OpenAIRE |
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