scholarly journals Mixed Periodontal Th1-Th2 Cytokine Profile in Actinobacillus actinomycetemcomitans-Specific Osteoprotegerin Ligand (or RANK-L)- Mediated Alveolar Bone Destruction In Vivo

2002 ◽  
Vol 70 (9) ◽  
pp. 5269-5273 ◽  
Author(s):  
Yen-Tung A. Teng
Keyword(s):  
Alveolar Bone ◽  
Bone Destruction ◽  
Actinobacillus Actinomycetemcomitans ◽  
Pcr Analysis ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Humanized Mouse Model ◽  
Periodontal Infection ◽  
Osteoprotegerin Ligand

ABSTRACT The Th1/Th2 cytokines involved in human periodontitis remain unclear; therefore, we established a humanized mouse model to investigate this issue in Actinobacillus actinomycetemcomitans-mediated periodontal infection. Quantitative-PCR analysis clearly demonstrates a predominantly mixed Th1 and Th2 expression profile associated with pathogen-specific cell-mediated immunity via osteoprotegerin ligand (or RANK-L)-mediated alveolar bone destruction in vivo.

scholarly journals Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection

2000 ◽  
Vol 106 (6) ◽  
pp. R59-R67 ◽  
Author(s):  
Yen-Tung A. Teng ◽  
Hai Nguyen ◽  
Xuijuan Gao ◽  
Young-Yun Kong ◽  
Reginald M. Gorczynski ◽  
...  
Keyword(s):  
T Cell ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
T Cell Immunity ◽  
Human T Cell ◽  
Cell Immunity ◽  
Periodontal Infection ◽  
Osteoprotegerin Ligand

scholarly journals Gamma Interferon Positively Modulates Actinobacillus actinomycetemcomitans-Specific RANKL+ CD4+ Th-Cell-Mediated Alveolar Bone Destruction In Vivo

2005 ◽  
Vol 73 (6) ◽  
pp. 3453-3461 ◽  
Author(s):  
Yen-Tung A. Teng ◽  
Deeqa Mahamed ◽  
Bhagirath Singh
Keyword(s):  
Signaling Pathways ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
Gamma Interferon ◽  
Actinobacillus Actinomycetemcomitans ◽  
Periodontal Tissues ◽  
Human T Cell ◽  
Th Cell ◽  
Ifn Γ

ABSTRACT Recent studies have shown the biological and clinical significance of signaling pathways of osteogenic cytokines RANKL-RANK/OPG in controlling osteoclastogenesis associated with bone pathologies, including rheumatoid arthritis, osteoporosis, and other osteolytic disorders. In contrast to the inhibitory effect of gamma interferon (IFN-γ) on RANKL-mediated osteoclastogenesis reported recently, alternative new evidence is demonstrated via studies of experimental periodontitis using humanized NOD/SCID and diabetic NOD mice and clinical human T-cell isolates from diseased periodontal tissues, where the presence of increasing IFN-γ is clearly associated with (i) enhanced Actinobacillus actinomycetemcomitans-specific RANKL-expressing CD4+ Th cell-mediated alveolar bone loss during the progression of periodontal disease and (ii) a concomitant and significantly increased coexpression of IFN-γ in RANKL(+) CD4+ Th cells. Therefore, there are more complex networks in regulating RANKL-RANK/OPG signaling pathways for osteoclastogenesis in vivo than have been suggested to date.

scholarly journals Induction of Genotype Cross-Reactive, Hepatitis C Virus-Specific, Cell-Mediated Immunity in DNA-Vaccinated Mice

2018 ◽  
Vol 92 (8) ◽  
pp. e02133-17 ◽  
Author(s):  
Danushka K. Wijesundara ◽  
Jason Gummow ◽  
Yanrui Li ◽  
Wenbo Yu ◽  
Benjamin J. Quah ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dna Vaccine ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Universal Vaccine ◽  
Cell Responses ◽  
Single Genotype

ABSTRACTA universal hepatitis C virus (HCV) vaccine should elicit multiantigenic, multigenotypic responses, which are more likely to protect against challenge with the range of genotypes and subtypes circulating in the community. A vaccine cocktail and vaccines encoding consensus HCV sequences are attractive approaches to achieve this goal. Consequently, in a series of mouse vaccination studies, we compared the immunogenicity of a DNA vaccine encoding a consensus HCV nonstructural 5B (NS5B) protein to that of a cocktail of DNA plasmids encoding the genotype 1b (Gt1b) and Gt3a NS5B proteins. To complement this study, we assessed responses to a multiantigenic cocktail regimen by comparing a DNA vaccine cocktail encoding Gt1b and Gt3a NS3, NS4, and NS5B proteins to a single-genotype NS3/4/5B DNA vaccine. To thoroughly evaluatein vivocytotoxic T lymphocyte (CTL) and T helper (Th) cell responses against Gt1b and Gt3a HCV peptide-pulsed target cells, we exploited a novel fluorescent-target array (FTA). FTA and enzyme-linked immunosorbent spot (ELISpot) analyses collectively indicated that the cocktail regimens elicited higher responses to Gt1b and Gt3a NS5B proteins than those with the consensus vaccine, while the multiantigenic DNA cocktail significantly increased the responses to NS3 and NS5B compared to those elicited by the single-genotype vaccines. Thus, a DNA cocktail vaccination regimen is more effective than a consensus vaccine or a monovalent vaccine at increasing the breadth of multigenotypic T cell responses, which has implications for the development of vaccines for communities where multiple HCV genotypes circulate.IMPORTANCEDespite the development of highly effective direct-acting antivirals (DAA), infections with hepatitis C virus (HCV) continue, particularly in countries where the supply of DAA is limited. Furthermore, patients who eliminate the virus as a result of DAA therapy can still be reinfected. Thus, a vaccine for HCV is urgently required, but the heterogeneity of HCV strains makes the development of a universal vaccine difficult. To address this, we developed a novel cytolytic DNA vaccine which elicits robust cell-mediated immunity (CMI) to the nonstructural (NS) proteins in vaccinated animals. We compared the immune responses against genotypes 1 and 3 that were elicited by a consensus DNA vaccine or a DNA vaccine cocktail and showed that the cocktail induced higher levels of CMI to the NS proteins of both genotypes. This study suggests that a universal HCV vaccine can most readily be achieved by use of a DNA vaccine cocktail.

scholarly journals Bone Resorption Caused by Three Periodontal Pathogens In Vivo in Mice Is Mediated in Part by Prostaglandin

1998 ◽  
Vol 66 (9) ◽  
pp. 4158-4162 ◽  
Author(s):  
Yuval Zubery ◽  
Colin R. Dunstan ◽  
Beryl M. Story ◽  
Lakshmyya Kesavalu ◽  
Jeffrey L. Ebersole ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Alveolar Bone ◽  
Tissue Injury ◽  
Bone Destruction ◽  
Fusobacterium Nucleatum ◽  
Host Responses ◽  
Periodontal Pathogens ◽  
Tissue Destruction

ABSTRACT Gingival inflammation, bacterial infection, alveolar bone destruction, and subsequent tooth loss are characteristic features of periodontal disease, but the precise mechanisms of bone loss are poorly understood. Most animal models of the disease require injury to gingival tissues or teeth, and the effects of microorganisms are thus complicated by host responses to tissue destruction. To determine whether three putative periodontal pathogens, Porphyromonas gingivalis, Campylobacter rectus, andFusobacterium nucleatum, could cause localized bone resorption in vivo in the absence of tissue injury, we injected live or heat-killed preparations of these microorganisms into the subcutaneous tissues overlying the calvaria of normal mice once daily for 6 days and then examined the bones histologically. We found that all three microorganisms (both live and heat killed) stimulated bone resorption and that the strain of F. nucleatum used appeared to be the strongest inducer of osteoclast activity. Treatment of the mice concomitantly with indomethacin reduced but did not completely inhibit bone resorption by these microorganisms, suggesting that their effects were mediated, in part, by arachidonic acid metabolites (e.g., prostaglandins). Our findings indicate that these potential pathogens can stimulate bone resorption locally when placed beside a bone surface in vivo in the absence of prior tissue injury and support a role for them in the pathogenesis of bone loss around teeth in periodontitis.

scholarly journals Gamma Interferon (IFN-γ) and IFN-γ-Inducing Cytokines Interleukin-12 (IL-12) and IL-18 Do Not Augment Infection-Stimulated Bone Resorption In Vivo

2004 ◽  
Vol 11 (1) ◽  
pp. 106-110 ◽  
Author(s):  
Hajime Sasaki ◽  
Khaled Balto ◽  
Nobuyuki Kawashima ◽  
Jean Eastcott ◽  
Katsuaki Hoshino ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Alveolar Bone ◽  
Interleukin 1 ◽  
Bone Destruction ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-γ) and IFN-γ-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12−/−, IL-18−/−, and IFN-γ−/− mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12−/−, IL-18−/−, and IFN-γ−/− mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-γ−/− mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1α levels. Recombinant IL-12, IL-18, and IFN-γ individually failed to consistently modulate macrophage IL-1α production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-γ do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways.

scholarly journals NIK inhibitor impairs chronic periodontitis via suppressing non-canonical NF-κB and osteoclastogenesis

2020 ◽  
Vol 78 (7) ◽  
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Lei Wang
Keyword(s):  
Alveolar Bone ◽  
Bone Destruction ◽  
Nuclear Factor Κb ◽  
Mice Model ◽  
Western Blot Assay ◽  
Beneficial Effects ◽  
Genes Expression ◽  
Receptor Activator

ABSTRACT Periodontitis is an inflammatory disease that causes damages to periodontium and alveolar bone. Overactivation and formation of osteoclasts can cause bone destruction, which contributes to periodontitis development. Receptor activator of nuclear factor κB ligand (RANKL)-mediated NF-κB signaling plays an essential role in osteoclasts differentiation. We aimed to study the effects of NIK-SMI1, an NF-κB-inducing kinase (NIK) inhibitor, on the osteoclastogenesis in vitro and periodontitis progression in vivo. A ligature-induced mice model of periodontitis was incorporated to test the potential therapeutic effect of NIK-SMI1 on periodontitis. The target protein and mRNA expression levels were determined by Western blot assay and real-time PCR assay, respectively. We found that the administration of NIK-SMI1 strongly inhibited the RANKL-stimulated non-canonical NF-κB signaling as demonstrated by decreased nuclear p52 expression and activity. Blocking NIK activity also resulted in reduced osteoclasts specific genes expression and enhanced IFN-β expression. NIK-SMI1 treatment resulted in attenuated periodontitis progression and pro-inflammatory cytokines expression in vivo. Our study suggested that NIK-SMI1 exerts beneficial effects on the mitigation of osteoclastogenesis in vitro and periodontitis progression in vivo. Application of NIK-SMI1 may serve as a potential therapeutic approach for periodontitis.

scholarly journals PF-3845, a Fatty Acid Amide Hydrolase Inhibitor, Directly Suppresses Osteoclastogenesis through ERK and NF-κB Pathways In Vitro and Alveolar Bone Loss In Vivo

2021 ◽  
Vol 22 (4) ◽  
pp. 1915
Author(s):  
Hye-Jung Ihn ◽  
Yi-Seul Kim ◽  
Soomin Lim ◽  
Jong-Sup Bae ◽  
Jae-Chang Jung ◽  
...  
Keyword(s):  
Bone Loss ◽  
Alveolar Bone ◽  
Fatty Acid Amide Hydrolase ◽  
Osteoclast Differentiation ◽  
Acid Amide ◽  
Bone Destruction ◽  
Alveolar Bone Loss ◽  
Nuclear Factor ◽  
Amide Hydrolase

Alveolar bone loss, the major feature of periodontitis, results from the activation of osteoclasts, which can consequently cause teeth to become loose and fall out; the development of drugs capable of suppressing excessive osteoclast differentiation and function is beneficial for periodontal disease patients. Given the difficulties associated with drug discovery, drug repurposing is an efficient approach for identifying alternative uses of commercially available compounds. Here, we examined the effects of PF-3845, a selective fatty acid amide hydrolase (FAAH) inhibitor, on receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclastogenesis, its function, and the therapeutic potential for the treatment of alveolar bone destruction in experimental periodontitis. PF-3845 significantly suppressed osteoclast differentiation and decreased the induction of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific markers. Actin ring formation and osteoclastic bone resorption were also reduced by PF-3845, and the anti-osteoclastogenic and anti-resorptive activities were mediated by the suppression of phosphorylation of rapidly accelerated fibrosarcoma (RAF), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase, (ERK) and nuclear factor κB (NF-κB) inhibitor (IκBα). Furthermore, the administration of PF-3845 decreased the number of osteoclasts and the amount of alveolar bone destruction caused by ligature placement in experimental periodontitis in vivo. The present study provides evidence that PF-3845 is able to suppress osteoclastogenesis and prevent alveolar bone loss, and may give new insights into its role as a treatment for osteoclast-related diseases.

scholarly journals Effect of lipopolysaccharide derived from surabaya isolates of Actinobacillus actinomycetemcomitans on alveolar bone destruction

2018 ◽  
Vol 11 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Rini Devijanti Ridwan ◽  
Sidarningsih ◽  
Tuti Kusumaningsih ◽  
Sherman Salim
Keyword(s):  
Alveolar Bone ◽  
Bone Destruction ◽  
Actinobacillus Actinomycetemcomitans

Immediate Loss of Cell-Mediated Immunity to Murine Cytomegalovirus upon Treatment with Immunosuppresive Agents

1980 ◽  
Vol 30 (3) ◽  
pp. 700-708
Author(s):  
Donald M. Mattsson ◽  
Richard J. Howard ◽  
Henry H. Balfour
Keyword(s):  
Cytomegalovirus Infection ◽  
Proliferative Response ◽  
Murine Cytomegalovirus ◽  
Cell Mediated Immunity ◽  
Blast Transformation ◽  
Specific Cell ◽  
Antilymphocyte Globulin ◽  
Prednisolone Treatment

Splenic lymphocytes from cytomegalovirus-infected mice lost their in vitro proliferative responses to cytomegalovirus antigen within 3 h after in vivo treatment with antilymphocyte globulin and prednisolone. The response was inhibited when the agents were administered separately or together, and inhibition persisted through a 2-week course of immunosuppression. Circulating specific antibodies were depressed by multiple injections of antilymphocyte globulin alone or with prednisolone, but not by prednisolone alone. Mitogen-induced blast transformation was immediately depressed by immunosuppression with both agents. Although the response to lipopolysaccharide returned briefly, it declined with continuing treatment. Cytomegalovirus infection augmented the depressive effect of immunosuppression on the lipopolysaccharide proliferative response. Prednisolone treatment of infected animals did not affect the concanavalin A response, and lipopolysaccharide stimulation decreased more slowly and to a lesser extent than it did in mice treated with antilymphocyte globulin or both agents. Loss of specific cell-mediated immunity and simultaneous depression of humoral immunity indicated that immunosuppression immediately created an inability to respond to an active cytomegalovirus infection.

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