Porphyromonas gingivalis induced up‐regulation of PD‐L1 in colon carcinoma cells. (19th May 2021)

• Record Type: Journal Article
• Authors: Adel‐Khattab, Doaa; Groeger, Sabine; Domann, Eugen; Chakraborty, Trinad; Lochnit, Günter; Meyle, Joerg
• Is Part Of: Molecular oral microbiology. Volume 36:Number 3(2021)
• Page Start: 172
• Page End: 181
• Publication Date: 2021-05-19
• Subjects: colon cancer -- Porphyromonas gingivalis -- programmed cell death; Mouth -- Microbiology -- Periodicals; Respiratory infections -- Microbiology -- Periodicals; Mouth -- Diseases -- Immunological aspects -- Periodicals; 617.522
• DOI: 10.1111/omi.12332
• Languages: English
• ISSNs: 2041-1006

Abstract

Abstract : Programmed death‐ligand‐1 (PD‐L1) is a ligand for programmed death receptor (PD‐1) that plays a major role in cell‐mediated immune response; it regulates T‐cell activation and regulates survival and functions of activated T cells. Expression of PD‐L1 can induce chronic inflammation and activate mechanisms of immune evasion. PD‐L1 is expressed in most of human carcinomas. Porphyromonas gingivalis ( P. gingivalis ) is a major keystone pathogen in periodontitis that invade host cells and disposes a variety of virulence factors. The aim of the present study was to clarify the signaling pathway of P. gingivalis molecules that induce PD‐L1 up‐regulation in colon carcinoma cells. Additionally, it was investigated which components of P. gingivalis are responsible for PD‐L1 induction. Colon cancer cells (CL‐11) were stimulated with total membrane (TM) fractions, peptidoglycans (PDGs) and viable P. gingivalis bacteria. Seven signaling molecule inhibitors were used: receptor‐interacting serine/threonine‐protein kinase 2 (RIP2) tyrosine kinase inhibitor, nucleotide‐binding oligomerization domain (NOD)‐like receptor 1&2 inhibitor, NOD‐like receptor, nuclear factor kappa B inhibitor, c‐Jun N‐terminal kinases inhibitor, mitogen‐activated protein/extracellular signal‐regulated kinase inhibitor, mitogen activated kinase (MAPK) inhibitor. PD‐L1 protein expression was examined by western blot analysis and quantitative real time PCR. It was demonstrated that the TM fraction and PDG induced up‐regulation of PD‐L1 expression in colon cancer cells. In conclusion, the results of this study suggest that PDG of P. gingivalis plays a major role in PD‐L1 up‐regulation in colon cancer cells. In addition, the mechanism of PD‐L1 up‐regulation depends on NOD 1 and NOD 2 and involves activation of RIP2 and MAPK signaling pathways.