Expression of interferon-γ, interferon-α and related genes in individuals with Down syndrome and periodontitis

Tanaka, Marcia Hiromi; Giro, Elisa María Aparecida; Cavalcante, Lícia Bezerra; Pires, Juliana Rico; Apponi, Luciano H.; Valentini, Sandro Roberto; Spolidório, Denise Madalena Palomari; Capela, Marisa Veiga; Rossa, Carlos; Scarel‐Caminaga, Raquel Mantuaneli

doi:10.1016/j.cyto.2012.08.020

Cited by 25 publications

(18 citation statements)

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“…The downregulation of the expression of mRNA encoding IRF-1 (12-fold) was comparable to the one observed elsewhere (8-fold) in gingival epithelial cells infected with P. gingivalis [25]. A significant reduction of the IRF-1 mRNA expression was also associated with DS patients compared to euploid individuals affected by periodontitis [31]. As IRF-1 regulated a diversity of cellular responses, the downregulation observed after infection of HGEC probably contributed to targeting genes possessing an interferon-stimulated response element within the promoter sequence, as demonstrated by the inhibition of cytokines IP-10, ITAC, and Mig expressions in epithelial cells [25].…”

Section: Discussionsupporting

confidence: 72%

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

Elkaïm

Bugueno

Benkirane‐Jessel

et al. 2017

Journal of Oral Microbiology

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Periodontitis is an inflammatory disease induced by pathogenic bacteria such as Porphyromonas gingivalis. Little is known about epidermal growth factor (EGF) signals in human gingival epithelial cells (HGEC), which are major targets of P. gingivalis, and how the expression of proteins participating in EGF signaling—that is, EGF-receptor (EGFR), suppressor of cytokine signaling-3 (SOCS-3), interferon regulatory factor-1 (IRF-1), and signal transducers and activators of transcription (STAT-3)—are modified. This study aimed to assess the effects of P. gingivalis and its purified lipopolysaccharide (LPS-Pg) on EGF signaling. HGEC were infected for 2 h in a dose-dependent manner with P. gingivalis and with heat-killed P. gingivalis, and activated for 2 and 24 h by 1 µg/mL of purified LPS-Pg. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to measure mRNA and protein levels for SOCS-3, IRF-1 EGF, EGFR, and STAT-3. The tyrosine-phosphorylation status of STAT-3 was also examined. The results showed that infection of HGEC cells with P. gingivalis, but not with heat-killed P. gingivalis, led to significant reductions in expression levels of mRNAs and proteins for SOCS-3, IRF-1, and EGFR, while LPS-Pg over time significantly increased the expression of these mRNAs and proteins. Tyrosine-phosphorylation of STAT-3 was significantly increased during infection with P. gingivalis and activation by LPS-Pg but not modified during infection with heat-killed P. gingivalis. This study highlights that P. gingivalis and its purified LPS differentially modulated the expression of proteins (SOCS-3, IRF-1, EGFR, and STAT-3) interfering with EGF signaling.

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Section: Discussionsupporting

confidence: 72%

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

Elkaïm

Bugueno

Benkirane‐Jessel

et al. 2017

Journal of Oral Microbiology

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“…The authors suggest that overexpression of RCAN1 in Down syndrome may alter downstream effector signalling in pathological ways. In support of this, reduced interleukin-10 and increased STAT3 pathway activation has been reported in Down syndrome [200,201].…”

Section: Genetic Influence Of Trisomy 21 On Immune System Disturbancementioning

confidence: 85%

What people with Down Syndrome can teach us about cardiopulmonary disease

Colvin

Yeager

2017

Eur Respir Rev

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Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations ( particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

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“…More recently, a study found global disruption of IFN-related gene networks in the brains of the Ts1Cje mouse model of DS, which also carries triplication of the IFN receptor subunits (Ling et al, 2014). However, deeper investigations of IFN signaling in human T21 cells and tissues are largely absent from the literature of the past 30 years, with a few exceptions, such as the description of IFN signaling as a contributor to periodontal disease in DS (Tanaka et al, 2012; Iwamoto et al, 2009). Collectively, these reports and the genomics analyses reported here demonstrate that activation of the IFN pathway in T21 cells is a widespread phenomenon that occurs in diverse tissues, and that is relevant to human Down syndrome as well as the various mouse models of DS with triplication of IFN receptors.…”

Section: Discussionmentioning

confidence: 99%

Trisomy 21 consistently activates the interferon response

Sullivan¹,

Lewis²,

Hill³

et al. 2016

eLife

268

261

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Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of the trisomy remain ill defined. Using complementary genomics analyses, we identified the interferon pathway as the major signaling cascade consistently activated by trisomy 21 in human cells. Transcriptome analysis revealed that trisomy 21 activates the interferon transcriptional response in fibroblast and lymphoblastoid cell lines, as well as circulating monocytes and T cells. Trisomy 21 cells show increased induction of interferon-stimulated genes and decreased expression of ribosomal proteins and translation factors. An shRNA screen determined that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts, and this defect is rescued by pharmacological JAK inhibition. Therefore, we propose that interferon activation, likely via increased gene dosage of the four interferon receptors encoded on chromosome 21, contributes to many of the clinical impacts of trisomy 21, and that interferon antagonists could have therapeutic benefits.DOI: http://dx.doi.org/10.7554/eLife.16220.001

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Expression of interferon-γ, interferon-α and related genes in individuals with Down syndrome and periodontitis

Cited by 25 publications

References 50 publications

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

Porphyromonas gingivalis and its lipopolysaccharide differently modulate epidermal growth factor–dependent signaling in human gingival epithelial cells

What people with Down Syndrome can teach us about cardiopulmonary disease

Trisomy 21 consistently activates the interferon response

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