Induction of B7-H1 receptor by bacterial cells fractions of Porphyromonas gingivalis on human oral epithelial cells: B7-H1 induction by Porphyromonas gingivalis fractions.
The immune-regulatory B7-H1 receptor, also known as programmed death-ligand 1 (PD-L1), plays an important role in cell-mediated immune response. It is a co-signaling molecule that mediates regulation of T cell activation and tolerance and is able to negatively regulate activated T cell functions and survival. High expression of B7-H1 in host cells may contribute to the chronicity of inflammatory disorders and represents a possible mechanism of immune evasion. Porphyromonas gingivalis is regarded as a keystone pathogen in periodontitis and is able to invade host cells and disposes a variety of virulence factors including lipopolysaccharide (LPS), fimbriae and proteases such as gingipains. Based on previous studies that demonstrated the capability of P. gingivalis to induce up-regulation of PD-L1 in malignant and non-malignant oral epithelial cells, the aim of the present work was to analyse the potential of various cellular components of P. gingivalis to induce the PD-L1 receptor. Human squamous carcinoma cells and primary gingival keratinocytes were stimulated with total, inner and outer membrane fractions, cytosolic proteins, as well as LPS and peptidoglycans. PD-L1 protein expression was investigated by Western blot analysis and RT-PCR. It was demonstrated that the total membrane fraction induced the highest up-regulation in B7-H1 expression, followed by the outer and inner membrane, whereas cytosolic proteins and LPS did not. In conclusion, we provide evidence that the membrane fraction of P. gingivalis is responsible for up-regulation of the immune-regulatory receptor PD-L1 in squamous carcinoma cells and gingival keratinocytes, and thus may support immune evasion of oral carcinomas.
Department of Periodontology, Justus-Liebig-University of Giessen, Germany. Electronic address: Sabine.E.Groeger@dentist.med.uni-giessen.de.
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Groeger
Department of Periodontology, Justus-Liebig-University of Giessen, Germany.
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Jarzina
Division of Structural Biochemistry, Research Center Borstel, Leibniz-Center for Medicine and Bioscience, Borstel, Germany.
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Mamat
Department of Periodontology, Justus-Liebig-University of Giessen, Germany.
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Meyle
D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D016866:Bacteroidaceae Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009061:Mouth Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D012333:RNA, Messenger; D007371:Interferon-gamma
B7-H1; Immune evasion; Immune-regulatory receptor; Porphyromonas gingivalis membrane