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 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 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 Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency

2006 ◽  
Vol 80 (1) ◽  
pp. 192-200 ◽  
Author(s):  
Ashley L. Steed ◽  
Erik S. Barton ◽  
Scott A. Tibbetts ◽  
Daniel L. Popkin ◽  
Mary L. Lutzke ◽  
...  
Keyword(s):  
Immune Surveillance ◽  
Viral Gene Expression ◽  
Gamma Interferon ◽  
Viral Gene ◽  
Herpesvirus Infection ◽  
Murine Gammaherpesvirus ◽  
Ifn Γ ◽  
Gammaherpesvirus 68 ◽  
Novel Strategy

ABSTRACT Establishment of latent infection and reactivation from latency are critical aspects of herpesvirus infection and pathogenesis. Interfering with either of these steps in the herpesvirus life cycle may offer a novel strategy for controlling herpesvirus infection and associated disease pathogenesis. Prior studies show that mice deficient in gamma interferon (IFN-γ) or the IFN-γ receptor have elevated numbers of cells reactivating from murine gammaherpesvirus 68 (γHV68) latency, produce infectious virus after the establishment of latency, and develop large-vessel vasculitis. Here, we demonstrate that IFN-γ is a powerful inhibitor of reactivation of γHV68 from latency in tissue culture. In vivo, IFN-γ controls viral gene expression during latency. Importantly, depletion of IFN-γ in latently infected mice results in an increased frequency of cells reactivating virus. This demonstrates that IFN-γ is important for immune surveillance that limits reactivation of γHV68 from latency.

scholarly journals Resistance to Acute Babesiosis Is Associated with Interleukin-12- and Gamma Interferon-Mediated Responses and Requires Macrophages and Natural Killer Cells

2003 ◽  
Vol 71 (4) ◽  
pp. 2002-2008 ◽  
Author(s):  
Irma Aguilar-Delfin ◽  
Peter J. Wettstein ◽  
David H. Persing
Keyword(s):  
Nk Cells ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
No Production ◽  
Cytokine Responses ◽  
Early Production ◽  
Ifn Γ ◽  
Crucial Part

ABSTRACT We examined the role of the cytokines gamma interferon (IFN-γ) and interleukin-12 (IL-12) in the model of acute babesiosis with the WA1 Babesia. Mice genetically deficient in IFN-γ-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WA1 Babesia, and observations were made on the course of infection and cytokine responses. Levels of IFN-γ and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-γ-mediated responses are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4+ T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4+ T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic Babesia WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-γ, and induction of macrophage-derived effector molecules like NO.

scholarly journals Management of Chronic Gingivitis with localized periodontitis by Nonsurgical (Phase I) Periodontal Therapy- A Case Report

2018 ◽  
Vol 7 (2) ◽  
pp. 33-37
Author(s):  
Md Huzzatul Islam Khan ◽  
Sultana Akter Eka ◽  
Md Ashif Iqbal
Keyword(s):  
Phase I ◽  
Oral Hygiene ◽  
Alveolar Bone ◽  
Bone Destruction ◽  
Chronic Inflammatory Disease ◽  
Periodontal Therapy ◽  
Periodontal Treatment ◽  
Periodontal Tissues ◽  
Hygiene Measures ◽  
Tissue Flap

Periodontitis is a chronic inflammatory disease of the periodontal tissues (periodontium) which surround and support the teeth, that results in attachment loss and alveolar bone destruction leads to ultimate tooth loss. It is caused by the bacteria present in dental plaque, which is a tenacious substance that forms on teeth and gingiva just after teeth are brushed. Periodontal treatment is aimed at controlling the infection in order to stop the progression of the disease and to be able to maintain a healthy periodontium. Mechanical debridement of supragingival and subgingival biofilms, together with adequate oral hygiene measures is the standard periodontal therapy. This mechanical subgingi- val biofilm debridement consists of an initial (nonsurgical /phase I) phase involving scaling and root planing (SRP) and the elimination of plaque retentive factors, followed by a surgical phase (if needed) including the elevation of a tissue flap and bone remodeling in further stages. The adjunct use of antibiotics has proven to additionally improve the outcome of periodontal treatment. A clinical case of a 40-years-old male patient with generalized severe chronic periodontitis with localized gingival swell- ing was treated with nonsurgical (phase I) periodontal therapy that was confined to oral hygiene instruction (OHI), SRP with an adjunct antimicrobial regimen.Update Dent. Coll. j: 2017; 7 (2): 33-37

scholarly journals A Signal Transducer and Activator of  Transcription (Stat)4-independent Pathway for the Development of  T Helper Type 1 Cells

1998 ◽  
Vol 188 (6) ◽  
pp. 1191-1196 ◽  
Author(s):  
Mark H. Kaplan ◽  
Andrea L. Wurster ◽  
Michael J. Grusby
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Th2 Cells ◽  
Signal Transducer ◽  
T Helper ◽  
Th1 Cell ◽  
Th Cells ◽  
Th Cell ◽  
Ifn Γ

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6−/− lymphocytes fail to differentiate into interleukin (IL)-4–secreting Th2 cells. However, in contrast to Stat4−/− lymphocytes, T cells from Stat4, Stat6−/− mice produce significant amounts of interferon (IFN)-γ when activated in vitro. Although Stat4, Stat6−/− lymphocytes produce less IFN-γ than IL-12–stimulated control lymphocytes, equivalent numbers of IFN-γ–secreting cells can be generated from cultures of Stat4, Stat6−/− lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell–promoting conditions. Moreover, Stat4, Stat6−/− mice are able to mount an in vivo Th1 cell–mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.

scholarly journals Development of a Human Gamma Interferon Enzyme Immunoassay and Comparison with Tuberculin Skin Testing for Detection ofMycobacterium tuberculosis Infection

1998 ◽  
Vol 5 (4) ◽  
pp. 531-536 ◽  
Author(s):  
Nuket Desem ◽  
Stephen L. Jones
Keyword(s):  
Enzyme Immunoassay ◽  
Skin Test ◽  
Skin Testing ◽  
Gamma Interferon ◽  
Tuberculin Skin Testing ◽  
In Vitro Test ◽  
Detection Range ◽  
Ifn Γ

ABSTRACT A sensitive two-step simultaneous enzyme immunoassay (EIA) for human gamma interferon (IFN-γ) has been developed and used as an in vitro test for human tuberculosis (TB) in comparison with tuberculin skin testing. The EIA was shown to be highly sensitive, detecting less than 0.5 IU of recombinant human IFN-γ per ml within a linear detection range of 0.5 to 150 IU/ml. The assay was highly reproducible and specific for native IFN-γ. In addition, the assay detected chimpanzee, orangutan, gibbon, and squirrel monkey IFN-γs. Cross-reactions with other human cytokines or with IFN-γs derived from mice, cattle, or Old World monkeys were not evident. The assay was used to detect TB infection by incubating whole blood overnight with human, avian, and bovine tuberculin purified protein derivatives (PPDs), as well as positive (mitogen)- and negative-control preparations. The levels of IFN-γ in plasma supernatants were then determined. Blood from 10 tuberculin skin test-positive individuals responded predominantly to the human tuberculin PPD antigen and to a lesser extent to bovine and avian PPD antigens. By contrast, blood from 10 skin test-negative individuals showed minimal responses or no response to any of the tuberculin PPDs. Detectable levels of IFN-γ were present in all blood samples stimulated with mitogen. In vivo tuberculin reactivity was correlated with IFN-γ responsiveness in vitro. These results support the further study of the blood culture–IFN-γ EIA system as an alternative to skin testing for the detection of human TB infection.

scholarly journals PTEN Inhibits Inflammatory Bone Loss in Ligature-Induced Periodontitis via IL1 and TNF-α

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chuanyun Fu ◽  
Zhimin Wei ◽  
Dongsheng Zhang
Keyword(s):  
Bone Remodeling ◽  
Alveolar Bone ◽  
Bone Erosion ◽  
Interleukin 1 ◽  
Inflammatory Factors ◽  
Oral Diseases ◽  
Periodontal Tissues ◽  
Tensin Homolog ◽  
Key Factor

Phosphatase and tensin homolog (PTEN) is a critical regulator of tumorigenesis and bone remodeling, which is also found expressed in the periodontal tissues. Periodontitis is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults. However, the functional relevance of PTEN in periodontitis remains unclear. Here, we report that PTEN plays an essential role in periodontitis. The in vivo results of our study showed a significant decrease of PTEN in the ligature-induced mouse periodontitis model. The function of PTEN in the macrophages was shown to be associated with inflammatory factors interleukin 1 (IL1) and tumor necrosis factor (TNF-α) by using overexpression and silence methods. Further mechanistic studies indicated lack of PTEN-activated IL1 and TNF-α, which increased the number of osteoclasts and led to alveolar bone erosion and loss. Moreover, PTEN nanoparticles could directly inhibit the inflammatory process and bone erosion, suggesting a controlling role of PTEN during bone remodeling. All these data identified the novel function of PTEN as a key factor in periodontitis and bone remodeling.

scholarly journals Lower Levels of Gamma Interferon Expressed by a Pseudotyped Single-Cycle Simian Immunodeficiency Virus Enhance Immunogenicity in Rats

2008 ◽  
Vol 83 (4) ◽  
pp. 1592-1601 ◽  
Author(s):  
Yue Peng ◽  
Fan-ching Lin ◽  
Paulo H. Verardi ◽  
Leslie A. Jones ◽  
Tilahun D. Yilma
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rat Model ◽  
Gamma Interferon ◽  
Fine Tuning ◽  
Vaccine Strategy ◽  
Single Cycle ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-γ) as a potential vaccine strategy. We previously showed that IFN-γ expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-γ had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-γ. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-γ (dSIVLRγ) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-γ (dSIVR). Rats vaccinated with dSIVLRγ also had lower viral loads than those vaccinated with dSIVR when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-γ (dSIVHRγ) did not further enhance immunity and was less protective than dSIVLRγ. In conclusion, the data indicated that IFN-γ functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-γ. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.

scholarly journals Inhibition of Apoptosis by Gamma Interferon in Cells and Mice Infected with Chlamydia muridarum (the Mouse Pneumonitis Strain of Chlamydia trachomatis)

2002 ◽  
Vol 70 (5) ◽  
pp. 2559-2565 ◽  
Author(s):  
Jean-Luc Perfettini ◽  
Toni Darville ◽  
Alice Dautry-Varsat ◽  
Roger G. Rank ◽  
David M. Ojcius
Keyword(s):  
Chlamydia Trachomatis ◽  
Inhibitory Effect ◽  
Gamma Interferon ◽  
Apoptotic Cells ◽  
Chlamydia Muridarum ◽  
Infected Cells ◽  
Heterogenous Population ◽  
Ifn Γ ◽  
In Cells

ABSTRACT The effect of gamma interferon (IFN-γ) on apoptosis due to infection by Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN-γ concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due to C. muridarum infection. In cells treated with an IFN-γ concentration that leads to the development of a heterogenous population of normal and aberrant Chlamydia vacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN-γ appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected with C. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN-γ-deficient mice. These results suggest that IFN-γ may contribute to pathogenesis of persistent Chlamydia infections in vivo by preventing apoptosis of infected cells.

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