Hemoglobin and LPS Act in Synergy to Amplify the Inflammatory Response

2007 ◽  
Vol 86 (9) ◽  
pp. 878-882 ◽  
Author(s):  
C. Bodet ◽  
F. Chandad ◽  
D. Grenier
Keyword(s):  
Gingival Crevicular Fluid ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Fusobacterium Nucleatum ◽  
Necrosis Factor Alpha ◽  
Vascular Disruption ◽  
Tnf Α ◽  
Factor Alpha ◽  
Crevicular Fluid ◽  
Lps Binding

Vascular disruption and bleeding during periodontitis likely increase the levels of hemoglobin in gingival crevicular fluid. The aim of this study was to investigate the effect of hemoglobin on the inflammatory responses of human macrophages stimulated with lipopolysaccharides (LPS) isolated from periodontopathogens. The production of interleukin-1 beta (IL-1β), IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) by macrophages following challenges with Porphyromonas gingivalis and Fusobacterium nucleatum LPS in the presence or absence of human hemoglobin was analyzed by ELISA. The effect of hemoglobin on LPS-binding to macrophages was evaluated with 3H-LPS. Hemoglobin and LPS from periodontopathogens acted in synergy to stimulate the production of high levels of IL-1β, IL-6, IL-8, and TNF-α by macrophages. Hemoglobin also enhanced LPS-binding to macrophages. This study suggests that hemoglobin contributes to increases in the levels of pro-inflammatory mediators in periodontal sites by acting in synergy with LPS from periodontopathogens, thus favoring the progression of periodontitis.

scholarly journals Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

2011 ◽  
Vol 79 (7) ◽  
pp. 2597-2607 ◽  
Author(s):  
Poonam Dharmani ◽  
Jaclyn Strauss ◽  
Christian Ambrose ◽  
Emma Allen-Vercoe ◽  
Kris Chadee
Keyword(s):  
Tumor Necrosis ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Mucin Secretion ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Colonic Cells ◽  
Necrosis Factor

ABSTRACTThe etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial speciesFusobacterium nucleatumis a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasiveF. nucleatumisolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only liveF. nucleatuminduced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasiveF. nucleatumisolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal thatF. nucleatummay represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

scholarly journals Periodontitis Vaccine Decreases Local Prostaglandin E2 Levels in a Primate Model

2004 ◽  
Vol 72 (2) ◽  
pp. 1166-1168 ◽  
Author(s):  
Frank A. Roberts ◽  
Laura S. Houston ◽  
Sheila A. Lukehart ◽  
Lloyd A. Mancl ◽  
G. Rutger Persson ◽  
...  
Keyword(s):  
Bone Loss ◽  
Gingival Crevicular Fluid ◽  
Prostaglandin E ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Periodontal Destruction ◽  
Factor Alpha ◽  
Crevicular Fluid ◽  
Necrosis Factor

ABSTRACT Interleukin-1β, tumor necrosis factor alpha, prostaglandin E2 (PGE2), and Porphyromonas gingivalis-specific immunoglobulin G levels in gingival crevicular fluid were measured in primates immunized with a P. gingivalis vaccine followed by ligature-induced periodontitis. Only PGE2 levels were dramatically suppressed (P < 0.0001) in immunized animals versus controls. A significant correlation (P < 0.027) was also found between PGE2 levels and decreased bone loss scores. This study presents the first evidence of a potential mechanism involved in periodontitis vaccine-induced suppression of bone loss in a nonhuman primate model and offers insight into the role of PGE2 in periodontal destruction.

Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

2019 ◽  
Vol 65 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Hong Xiao Cui ◽  
Xiu Rong Xu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Intestinal Bacteria ◽  
Inflammatory Factors ◽  
Rabbit Ileum ◽  
Necrosis Factor Alpha ◽  
Heat Treated ◽  
Tnf Α ◽  
Factor Alpha ◽  
Anti Inflammatory

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

scholarly journals Interaction of Neisseria meningitidis with Human Dendritic Cells

2001 ◽  
Vol 69 (11) ◽  
pp. 6912-6922 ◽  
Author(s):  
Annette Kolb-Mäurer ◽  
Alexandra Unkmeir ◽  
Ulrike Kämmerer ◽  
Claudia Hübner ◽  
Thomas Leimbach ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Neisseria Meningitidis ◽  
Proinflammatory Cytokines ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Necrosis Factor

ABSTRACT Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-α, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1β, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.

scholarly journals Moesin Functions as a Lipopolysaccharide Receptor on Human Monocytes

1999 ◽  
Vol 67 (7) ◽  
pp. 3215-3220 ◽  
Author(s):  
Ziad N. Tohme ◽  
Salomon Amar ◽  
Thomas E. Van Dyke
Keyword(s):  
Interleukin 1 ◽  
Biologically Active ◽  
Sequence Motif ◽  
Human Monocytes ◽  
Tissue Destruction ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Tnf Α ◽  
Partial Blocking ◽  
Lps Binding

ABSTRACT Bacterial endotoxin (lipopolysaccharide [LPS]), a glycolipid found in the outer membranes of gram-negative bacteria, induces the secretion of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and IL-6 by monocytes/macrophages. The secretion of these biologically active compounds leads to multiple pathological conditions, such as septic shock. There is substantial evidence that chronic exposure to LPS mediates, at least in part, the tissue destruction associated with gram-negative infection. CD14, a 55-kDa protein, has been identified as an LPS receptor. In conjunction with a serum protein, LPS binding protein (LBP), LPS-CD14 interactions mediate many LPS functions in the inflammatory response. However, CD14 lacks a cytoplasmic domain, or any known signal transduction sequence motif, suggesting the existence of another cell surface domain capable of transducing signals. In this paper, we report a second, CD14-independent LPS binding site, which, based on biological activity, appears to be a functional LPS receptor. Cross-linking experiments were performed to identify LPS binding sites. Two molecules were identified: a 55-kDa protein (CD14) and a second, 78-kDa band. Sequencing of the 78-kDa protein by mass spectroscopic analysis revealed 100% homology with moesin (membrane-organizing extension spike protein). Antibody to CD14 induced partial blocking of the LPS response. However, antimoesin monoclonal antibody completely blocked the LPS-induced TNF-α response in human monocytes, without blocking CD14 binding of LPS. Irrelevant isotype controls had no effect. Additional experiments were performed to evaluate the specificity of the antimoesin blocking. Separate experiments evaluated antimoesin effects on monocyte chemotaxis, IL-1 production in response to IL-1 stimulation, and TNF-α secretion in response toStaphylococcus aureus stimulation. Antimoesin blocked only LPS-mediated events. The data suggest that moesin functions as an independent LPS receptor on human monocytes. The role of moesin in transduction of CD14-mediated signals is discussed.

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