Contrasting Roles of IFN-γ in Murine Models of Autoimmune Thyroid Diseases

Fang, Yujiang; Yu, Shiguang; Braley‐Mullen, Helen

doi:10.1089/thy.2007.0261

Cited by 19 publications

(14 citation statements)

References 71 publications

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“…IFN- γ, a prototypic proinflammatory cytokine produced by several different cell types, including the Th1 subset of CD4(+) T cells, plays an important role in inflammation and autoimmune diseases [13]. Carella C et al observed that INF- γ is the cytokine most clearly associated with AITD, especially hypothyroidism, despite being neither Th1- nor Th2-dependent [14].…”

Section: Discussionmentioning

confidence: 99%

Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

et al. 2011

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BackgroundIn recent few years is underlined that altered balance of pro- and anti-inflammatory cytokines play an important role in the pathogenesis of AITD.The aim of this study was to estimate intracellular INF-γ and IL-4 levels in thyroid-infiltrating lymphocytes and thyrocytes isolated from thyroid tissues in 54 adolescent patients aged 8-21 years, with Graves' disease (GD; n = 18), Hashimoto's thyroiditis (HT; n = 18) and non-toxic multinodular goiter (NTMG; n = 18).MethodsFresh thyroid tissues were taken on culture medium RPMI -1640, it was mechanically prepared. In next step were added cell activators -12- myristate 13- the acetate (PMA) and Ionomycin as well as the inhibitor of transportation of proteins - Breferdin A. They were cultured 24 hours in 50 ml flasks at 37°C in a 5-95% CO2-air water-saturated atmosphere. After that, thyrocytes were identified by mouse mAb directed against human TPO epitope 64 conjugated with rabbit anti-mouse antibodies IgG (Fab')2 labeled by FITC. After incubation at room temperature to each of samples added reagent A fixative the cellular membrane. In next step into the cell suspensions were added reagent B to permeabilization of cellular membrane and specific anti-IL-4-PE or anti-IFN-γ-PE mAbs. Identification of intracellular cytokines in T lymphocytes was performed in the same procedure with application of anti-CD4-PerCP and anti-CD8-PerCP mAbs specific for T lymphocytes. The cells were analyzed in a flow cytometry (Coulter EPICS XL).ResultsIn examined group of patients with GD we observed statistically significant higher mean percentage of cells with phenotype CD4+IL-4 (p < 0.05; p < 0.025), CD8+IL-4 (p < 0.033; p < 0.01) and TFCs-IL-4+ (p < 0.05; p < 0.01) in comparison to patients with HT and NTMG. The analysis of mean percentages of positive TILs and TFCs with intracellular INF-g levels in patients with HT revealed statistically significant increase percentage of CD4+INF-γ (p < 0.04; p < 0.001), CD8+ INF-γ (NS; p < 0.025), TFCs+INF-γ (p < 0.03; p < 0.001) cells in comparison to the percentage of positive cells from patients with GD and NTMG.ConclusionsWe conclude that human thyrocytes in autoimmune thyroid disorders could be a source of cytokine production and that their activation influences local interaction with T lymphocytes inflowing to the thyroid gland.

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Section: Discussionmentioning

confidence: 99%

Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

et al. 2011

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“…In addition to Lxs, there are a host of other soluble mediators and cells central to resolution whose expression/synthesis occurs at strategic checkpoints throughout inflammation to switch the response off and restore homeostasis (12)(13)(14)(15)(16)(17). Although the sequential activation of these proresolution pathways has almost exclusively been elucidated using inbred rodents, little is known about their role in limiting inflammatory responses in humans.…”

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confidence: 99%

Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways

Morris

Stables

Colville‐Nash

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

101

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Lipoxins (Lxs) and aspirin-triggered epi-Lxs (15-epi-LxA 4 ) act through the ALX/FPRL1 receptor to block leukocyte trafficking, dampen cytokine/chemokine synthesis, and enhance phagocytic clearance of apoptotic leukocytes-key requisites for inflammatory resolution. Although studies using primarily inbred rodents have highlighted resolution as an active event, little is known about the role resolution pathways play in controlling the duration/profile of inflammatory responses in humans. To examine this, we found two types of responders to cantharidin-induced skin blisters in male healthy volunteers: those with immediate leukocyte accumulation and cytokine/chemokine synthesis followed by early resolution and a second group whose inflammation increased gradually over time followed by delayed resolution. In early resolvers, blister 15-epiLxA 4 and leukocyte ALX were low, but increased as inflammation abated. In contrast, in delayed resolvers, 15-epi-LxA 4 and ALX were high early in the response but waned as inflammation progressed. Elevating 15-epi-LxA 4 in early resolvers using aspirin increased blister leukocyte ALX but reduced cytokines/chemokines as well as polymorphonuclear leukocyte and macrophage numbers. These findings show that two phenotypes exist in humans with respect to inflammation severity/longevity controlled by proresolution mediators, namely 15-epi-LxA 4 . These data have implications for understanding the etiology of chronic inflammation and future directions in antiinflammatory therapy.eicosanoids | inflammation | leukocytes

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“…In other experiments using lung epithelia, activation of inducible nitric oxide (NO) synthase (iNOS) by IRF-1 led to a subsequent NO-induced activation of CFTR (12,36). IFN␥ has been implicated in the pathogenesis of a number of inflammatory diseases of infectious or presumed autoimmune origin (13,19,74). In the eye, IFN␥ has been detected in vitreous aspirates of patients with uveitis, proliferative vitreoretinopathy, and other inflammatory ocular diseases (21,26,40,51).…”

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confidence: 99%

IFNγ regulates retinal pigment epithelial fluid transport

Maminishkis

Banzon

et al. 2009

American Journal of Physiology-Cell Physiology

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The present experiments show that IFNgamma receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption. These effects are mediated through JAK-STAT and p38 MAPK signaling pathways. Second messenger signaling through cAMP-PKA pathway- and interferon regulatory factor-1-dependent production of nitric oxide/cGMP stimulated the CFTR at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFNgamma applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space between the retinal photoreceptors and RPE. Removal of this extra fluid was blocked by a combination of PKA and JAK-STAT pathway inhibitors injected into the subretinal space. These results demonstrate a protective role for IFNgamma in regulating retinal hydration across the outer blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.

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Contrasting Roles of IFN-γ in Murine Models of Autoimmune Thyroid Diseases

Cited by 19 publications

References 71 publications

Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

Cytometric evaluation of intracellular IFN-γ and IL-4 levels in thyroid follicular cells from patients with autoimmune thyroid diseases

Dichotomy in duration and severity of acute inflammatory responses in humans arising from differentially expressed proresolution pathways

IFNγ regulates retinal pigment epithelial fluid transport

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