Interaction between PKR and PACT mediated by LPS‐inducible NF‐κB in human gingival cells

Yoshida, Kaya; Okamura, Hirohiko; Hoshino, Yumi; Shono, Masayuki; Yoshioka, Masami; Hinode, Daisuke; Yoshida, Hideo

doi:10.1002/jcb.23340

Cited by 8 publications

(3 citation statements)

References 29 publications

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“…So, we also focused on the LPS and TLR4 systems in LX-2 cells. It is known that LPS treatment upregulates PACT expression [ 41 ], but we did not observe any differences in miR-122 expression between HSCs treated with or without LPS (1.1 or 1.0-fold, respectively).…”

Section: Discussioncontrasting

confidence: 79%

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MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells

et al. 2015

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MicroRNA-122 (miR-122) is one of the most abundant miRs in the liver. Previous studies have demonstrated that miR-122 plays a role in inflammation in the liver and functions in hepatic stellate cells (HSCs), which reside in the space of Disse. Here, we showed that the transient inhibition of PKR-activating protein (PACT) expression, by miR-122 or siRNA targeting of PACT, suppressed the production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and IL-1β, in human HSC LX-2. Sequence and functional analyses confirmed that miR-122 directly targeted the 3′-untranslated region of PACT. Immunofluorescence analysis revealed that miR-122 blocked NF-κB-nuclear translocation in LX-2 cells. We also showed that conditioned medium from miR-122-transfected LX-2 cells suppressed human monocyte-derived THP-1 cell migration. Taken together, our study indicates that miR-122 may downregulate cytokine production in HSCs and macrophage chemotaxis and that the targeting of miR-122 may have therapeutic potential for preventing the progression of liver diseases.

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Section: Discussioncontrasting

confidence: 79%

“…PACT is activated by bacterial products and cellular stress [ 40 ]. Yoshida et al [ 41 ] have reported that PACT-PKR interaction and phosphorylation of PKR are associated with the induction of NF-κB by LPS. Treatment of PKR inhibitor C16 prevented activation of NF-κB [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells

et al. 2015

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“…The role of PKR in inflammation appears to be dependent on both context and cell type (Yoshida et al. ; Watanabe et al. ).…”

Section: Introductionmentioning

confidence: 99%

Imoxin attenuates LPS‐induced inflammation and MuRF1 expression in mouse skeletal muscle

et al. 2018

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The double‐stranded RNA‐dependent protein kinase (PKR) contributes to inflammatory cytokine expression and disease pathogenesis in many conditions. Limited data are available on the efficacy of the PKR inhibitor imoxin to prevent lipopolysaccharide (LPS)‐induced inflammation in skeletal muscle in vivo. The aim of this study was to evaluate the effect of imoxin, a PKR inhibitor, on inflammatory and atrophy signaling in skeletal muscle in response to an acute inflammatory insult with LPS. Six‐week old C57BL/6J mice received vehicle (saline) or 0.5 mg/kg imoxin 24 and 2 h prior to induction of inflammation via 1 mg/kg LPS. Gastrocnemius muscles were collected 24 h post‐LPS and mRNA and protein expression were assessed. LPS lead to a loss of body weight, which was similar in Imoxin+LPS. There were no differences in muscle weight among groups. LPS increased gastrocnemius mRNA expression of TNF‐α and IL‐1β, and protein levels of NLRP3, all of which were attenuated by imoxin. Similarly, IL‐6 mRNA and IL‐1β protein were suppressed in Imoxin+LPS compared to LPS alone. LPS increased mRNA of the atrogenes, MuRF1 and MAFbx, and imoxin attenuated the LPS‐induced increase in MuRF1 mRNA, and lowered MuRF1 protein. Imoxin+LPS increased p‐Akt compared to saline or LPS, whereas p‐mTOR was unaltered. FoxO1 was upregulated and p‐FoxO1/FoxO1 reduced by LPS, both of which were prevented by imoxin. Both LPS and Imoxin+LPS had diminished p‐FoxO3/FoxO3 compared to control. These results demonstrate the potential anti‐inflammatory and anti‐atrophy effects of imoxin on skeletal muscle in vivo.

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The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions

et al. 2017

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Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

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Interaction between PKR and PACT mediated by LPS‐inducible NF‐κB in human gingival cells

Cited by 8 publications

References 29 publications

MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells

MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells

Imoxin attenuates LPS‐induced inflammation and MuRF1 expression in mouse skeletal muscle

The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions

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