Glycated albumin produced in diabetic hyperglycemia promotes monocyte secretion of inflammatory cytokines and bacterial adherence to epithelial cells

E. Shim, Jegdish Babu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background and Objective: The prevalence and severity of periodontal disease increase in patients with insulin-deficient or insulin-resistant forms of diabetes. A common characteristic of diabetes is the presence of hyperglycemia. A critical consequence of hyperglycemia is the nonenzymatic glycation and oxidation of proteins and lipids, resulting in the irreversible formation of advanced glycation end-products (AGEs). A central means by which AGEs are believed to impart their pathogenic effects is via interacting with specific cellular receptors; the best-characterized of these is receptor for AGE (RAGE). The major consequences of the AGE-RAGE interaction are the generation of enhanced cellular oxidant stress, hypersecretion of inflammatory mediators and altered subgingival flora. The aim of this study was to elucidate the influence of glycated albumin (G-alb), with or without lipopolysaccharide (LPS) isolated from periodontal pathogens, on the secretion of inflammatory cytokines by cultured monocytic cells and also to investigate the role of G-alb in adherence of bacteria to epithelial cells. Material and Methods: Activated THP-1 cells (1 × 106 cells) were incubated for 24 h with G-alb or normal albumin (N-alb), with or without LPS isolated from two periodontal pathogens. Supernatant fluids were collected and assayed for the cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ELISA. For bacterial adhesion assays, S-G epithelial cells were grown on cover slips and incubated with G-alb (10 μg/mL) or N-alb (control) for 30 min. The cover slips were rinsed and then incubated with bacteria for 2 h. The number of adherent bacteria was determined by counting 20 epithelial cells chosen randomly under a light microscope. Results: The secretion of IL-1β, TNF-α and IL-6 by THP-1 cells was greater in the presence of G-alb than in the presence of N-alb. The amounts of cytokines secreted were even greater when THP-1 cells were incubated with G-alb and LPS of periodontal pathogens. The effect of G-alb and LPS was reduced when RAGE was blocked by its antibody. Coating the cultured epithelial cells with G-alb resulted in increased bacterial adherence. Conclusion: This study demonstrated the role of G-alb in stimulating cultured monocytic cells to secrete inflammatory cytokines. The stimulation was found to be greater when cells were incubated with LPS in addition to G-alb. The over-expression of inflammatory cytokines as a result of the combined effects of G-alb and bacterial LPS may contribute to the severity of periodontal disease in diabetic subjects.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalJournal of Periodontal Research
Volume50
Issue number2
DOIs
StatePublished - Jan 1 2015

Fingerprint

Hyperglycemia
Monocytes
Epithelial Cells
Cytokines
Lipopolysaccharides
Albumins
Cultured Cells
Advanced Glycosylation End Products
Periodontal Diseases
Bacteria
Interleukin-1beta
Interleukin-6
glycosylated serum albumin
Tumor Necrosis Factor-alpha
Insulin
Bacterial Adhesion
Gastrin-Secreting Cells
Oxidants
Enzyme-Linked Immunosorbent Assay
Lipids

All Science Journal Classification (ASJC) codes

  • Periodontics

Cite this

@article{ff871505a5fc45079f7cd76cb18b2665,
title = "Glycated albumin produced in diabetic hyperglycemia promotes monocyte secretion of inflammatory cytokines and bacterial adherence to epithelial cells",
abstract = "Background and Objective: The prevalence and severity of periodontal disease increase in patients with insulin-deficient or insulin-resistant forms of diabetes. A common characteristic of diabetes is the presence of hyperglycemia. A critical consequence of hyperglycemia is the nonenzymatic glycation and oxidation of proteins and lipids, resulting in the irreversible formation of advanced glycation end-products (AGEs). A central means by which AGEs are believed to impart their pathogenic effects is via interacting with specific cellular receptors; the best-characterized of these is receptor for AGE (RAGE). The major consequences of the AGE-RAGE interaction are the generation of enhanced cellular oxidant stress, hypersecretion of inflammatory mediators and altered subgingival flora. The aim of this study was to elucidate the influence of glycated albumin (G-alb), with or without lipopolysaccharide (LPS) isolated from periodontal pathogens, on the secretion of inflammatory cytokines by cultured monocytic cells and also to investigate the role of G-alb in adherence of bacteria to epithelial cells. Material and Methods: Activated THP-1 cells (1 × 106 cells) were incubated for 24 h with G-alb or normal albumin (N-alb), with or without LPS isolated from two periodontal pathogens. Supernatant fluids were collected and assayed for the cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ELISA. For bacterial adhesion assays, S-G epithelial cells were grown on cover slips and incubated with G-alb (10 μg/mL) or N-alb (control) for 30 min. The cover slips were rinsed and then incubated with bacteria for 2 h. The number of adherent bacteria was determined by counting 20 epithelial cells chosen randomly under a light microscope. Results: The secretion of IL-1β, TNF-α and IL-6 by THP-1 cells was greater in the presence of G-alb than in the presence of N-alb. The amounts of cytokines secreted were even greater when THP-1 cells were incubated with G-alb and LPS of periodontal pathogens. The effect of G-alb and LPS was reduced when RAGE was blocked by its antibody. Coating the cultured epithelial cells with G-alb resulted in increased bacterial adherence. Conclusion: This study demonstrated the role of G-alb in stimulating cultured monocytic cells to secrete inflammatory cytokines. The stimulation was found to be greater when cells were incubated with LPS in addition to G-alb. The over-expression of inflammatory cytokines as a result of the combined effects of G-alb and bacterial LPS may contribute to the severity of periodontal disease in diabetic subjects.",
author = "E. Shim and Jegdish Babu",
year = "2015",
month = "1",
day = "1",
doi = "10.1111/jre.12194",
language = "English (US)",
volume = "50",
pages = "197--204",
journal = "Journal of Periodontal Research",
issn = "0022-3484",
publisher = "Blackwell Munksgaard",
number = "2",

}

TY - JOUR

T1 - Glycated albumin produced in diabetic hyperglycemia promotes monocyte secretion of inflammatory cytokines and bacterial adherence to epithelial cells

AU - Shim, E.

AU - Babu, Jegdish

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background and Objective: The prevalence and severity of periodontal disease increase in patients with insulin-deficient or insulin-resistant forms of diabetes. A common characteristic of diabetes is the presence of hyperglycemia. A critical consequence of hyperglycemia is the nonenzymatic glycation and oxidation of proteins and lipids, resulting in the irreversible formation of advanced glycation end-products (AGEs). A central means by which AGEs are believed to impart their pathogenic effects is via interacting with specific cellular receptors; the best-characterized of these is receptor for AGE (RAGE). The major consequences of the AGE-RAGE interaction are the generation of enhanced cellular oxidant stress, hypersecretion of inflammatory mediators and altered subgingival flora. The aim of this study was to elucidate the influence of glycated albumin (G-alb), with or without lipopolysaccharide (LPS) isolated from periodontal pathogens, on the secretion of inflammatory cytokines by cultured monocytic cells and also to investigate the role of G-alb in adherence of bacteria to epithelial cells. Material and Methods: Activated THP-1 cells (1 × 106 cells) were incubated for 24 h with G-alb or normal albumin (N-alb), with or without LPS isolated from two periodontal pathogens. Supernatant fluids were collected and assayed for the cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ELISA. For bacterial adhesion assays, S-G epithelial cells were grown on cover slips and incubated with G-alb (10 μg/mL) or N-alb (control) for 30 min. The cover slips were rinsed and then incubated with bacteria for 2 h. The number of adherent bacteria was determined by counting 20 epithelial cells chosen randomly under a light microscope. Results: The secretion of IL-1β, TNF-α and IL-6 by THP-1 cells was greater in the presence of G-alb than in the presence of N-alb. The amounts of cytokines secreted were even greater when THP-1 cells were incubated with G-alb and LPS of periodontal pathogens. The effect of G-alb and LPS was reduced when RAGE was blocked by its antibody. Coating the cultured epithelial cells with G-alb resulted in increased bacterial adherence. Conclusion: This study demonstrated the role of G-alb in stimulating cultured monocytic cells to secrete inflammatory cytokines. The stimulation was found to be greater when cells were incubated with LPS in addition to G-alb. The over-expression of inflammatory cytokines as a result of the combined effects of G-alb and bacterial LPS may contribute to the severity of periodontal disease in diabetic subjects.

AB - Background and Objective: The prevalence and severity of periodontal disease increase in patients with insulin-deficient or insulin-resistant forms of diabetes. A common characteristic of diabetes is the presence of hyperglycemia. A critical consequence of hyperglycemia is the nonenzymatic glycation and oxidation of proteins and lipids, resulting in the irreversible formation of advanced glycation end-products (AGEs). A central means by which AGEs are believed to impart their pathogenic effects is via interacting with specific cellular receptors; the best-characterized of these is receptor for AGE (RAGE). The major consequences of the AGE-RAGE interaction are the generation of enhanced cellular oxidant stress, hypersecretion of inflammatory mediators and altered subgingival flora. The aim of this study was to elucidate the influence of glycated albumin (G-alb), with or without lipopolysaccharide (LPS) isolated from periodontal pathogens, on the secretion of inflammatory cytokines by cultured monocytic cells and also to investigate the role of G-alb in adherence of bacteria to epithelial cells. Material and Methods: Activated THP-1 cells (1 × 106 cells) were incubated for 24 h with G-alb or normal albumin (N-alb), with or without LPS isolated from two periodontal pathogens. Supernatant fluids were collected and assayed for the cytokines interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ELISA. For bacterial adhesion assays, S-G epithelial cells were grown on cover slips and incubated with G-alb (10 μg/mL) or N-alb (control) for 30 min. The cover slips were rinsed and then incubated with bacteria for 2 h. The number of adherent bacteria was determined by counting 20 epithelial cells chosen randomly under a light microscope. Results: The secretion of IL-1β, TNF-α and IL-6 by THP-1 cells was greater in the presence of G-alb than in the presence of N-alb. The amounts of cytokines secreted were even greater when THP-1 cells were incubated with G-alb and LPS of periodontal pathogens. The effect of G-alb and LPS was reduced when RAGE was blocked by its antibody. Coating the cultured epithelial cells with G-alb resulted in increased bacterial adherence. Conclusion: This study demonstrated the role of G-alb in stimulating cultured monocytic cells to secrete inflammatory cytokines. The stimulation was found to be greater when cells were incubated with LPS in addition to G-alb. The over-expression of inflammatory cytokines as a result of the combined effects of G-alb and bacterial LPS may contribute to the severity of periodontal disease in diabetic subjects.

UR - http://www.scopus.com/inward/record.url?scp=84923846001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923846001&partnerID=8YFLogxK

U2 - 10.1111/jre.12194

DO - 10.1111/jre.12194

M3 - Article

VL - 50

SP - 197

EP - 204

JO - Journal of Periodontal Research

JF - Journal of Periodontal Research

SN - 0022-3484

IS - 2

ER -