Protection of Lipopolysaccharide (LPS) Preconditioning against Endotoxin-Induced Uveitis (EIU) in Rats is Associated with Overexpression of Interleukin-1 Receptor-Associated Kinase M (IRAK-M)

Yu, Shuo; Liu, Xinli; Zhang, Nan; Yang, Shuo; Mao, Cui; Feng, Shilan; Hong, Lü

doi:10.1080/09273948.2017.1291842

Cited by 8 publications

(16 citation statements)

References 23 publications

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“…Of the 49 included in vivo studies, 12 studies reported data from experiments performed using in vivo human model [ 45 , 50 – 60 ], 34 studies [ 29 , 32 , 36 – 41 , 43 , 61 – 85 ] used rodents (mice or rats), and the remaining three used sheep [ 44 ], cows [ 86 ] or pigs [ 42 ]. All included human studies (12 studies) used LPS administration with in vivo doses of 2–4 ng/kg.…”

Section: Resultsmentioning

confidence: 99%

“…Of included studies, there were 20 studies (12 mouse studies and 8 human studies) in which two-challenge intervention was performed [ 29 , 36 , 38 , 39 , 42 – 45 , 51 , 52 , 54 , 55 , 58 – 64 , 86 ]; and nine studies made use of IRAK3 gene knockout or silencing [ 32 , 36 – 41 , 67 , 68 ]. Most studies (44 studies) measured outcomes at intervals ranging between 1h and 72h following the first challenge, while several studies measured outcomes at 5d [ 43 ], 7d [ 44 , 59 , 67 , 68 ], 10d [ 86 ], or 14d [ 42 ]. After the second challenge, outcomes of interest were measured between 2h and 24h.…”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analyses of interleukin-1 receptor associated kinase 3 (IRAK3) action on inflammation in in vivo models for the study of sepsis

et al. 2022

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Background Interleukin-1 receptor associated kinase 3 (IRAK3) is a critical modulator of inflammation and is associated with endotoxin tolerance and sepsis. Although IRAK3 is known as a negative regulator of inflammation, several studies have reported opposing functions, and the temporal actions of IRAK3 on inflammation remain unclear. A systematic review and meta-analyses were performed to investigate IRAK3 expression and its effects on inflammatory markers (TNF-α and IL-6) after one- or two-challenge interventions, which mimic the hyperinflammatory and immunosuppression phases of sepsis, respectively, using human or animal in vivo models. Methods This systematic review and meta-analyses has been registered in the Open Science Framework (OSF) (Registration DOI: 10.17605/OSF.IO/V39UR). A systematic search was performed to identify in vivo studies reporting outcome measures of expression of IRAK3 and inflammatory markers. Meta-analyses were performed where sufficient data was available. Results The search identified 7778 studies for screening. After screening titles, abstracts and full texts, a total of 49 studies were included in the systematic review. The review identified significant increase of IRAK3 mRNA and protein expression at different times in humans compared to rodents following one-challenge, whereas the increases of IL-6 and TNF-α protein expression in humans were similar to rodent in vivo models. Meta-analyses confirmed the inhibitory effect of IRAK3 on TNF-α mRNA and protein expression after two challenges. Conclusions A negative correlation between IRAK3 and TNF-α expression in rodents following two challenges demonstrates the association of IRAK3 in the immunosuppression phase of sepsis. Species differences in underlying biology affect the translatability of immune responses of animal models to human, as shown by the dissimilarity in patterns of IRAK3 mRNA and protein expression between humans and rodents following one challenge that are further influenced by variations in experimental procedures.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A systematic review and meta-analyses of interleukin-1 receptor associated kinase 3 (IRAK3) action on inflammation in in vivo models for the study of sepsis

et al. 2022

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“…Here, TLR4-signaling and its possible alteration via preconditioning might play an important role [22,23]. Inflammatory preconditioning has also been investigated in contexts of inflammation after stroke or spinal cord injury where neuroprotective effects have been shown [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

Heinz

Brandenburg

Nieminen-Kelhä

et al. 2021

J Neuroinflammation

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Background Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. Methods 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. Results Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. Conclusions Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity.

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“…The body becomes tolerant to subsequent exposure to a lethal dose of LPS and tissue damage caused by inflammatory reaction is significantly reduced; this phenomenon is called endotoxin tolerance (ET) [6]. Accumulating evidences [7,8] show that a low dose of LPS pretreatment can relieve the intraocular inflammation in EIU rats. This protective effect is associated with changes of PI3K/AKT pathway and upregulation of IRAK-M, which is mediated by TLR4 signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Low Dose of Lipopolysaccharide Pretreatment on Endotoxin-Induced Uveitis in Rats Is Associated with Downregulation of CSF-1 and Upregulation of LRR-1

Ling

Wang

et al. 2020

Journal of Immunology Research

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Purpose. To observe the effect of low dose of lipopolysaccharide (LPS) pretreatment on the expression of CSF-1 and LRR-1 in rats with endotoxin-induced uveitis (EIU), and to explore the possible role of TLR4. Method. EIU was induced by a single subcutaneous injection of 200 μg LPS. For the endotoxin tolerance group, the induction of EIU was preceded by a daily subcutaneous injection of 0.1 mg/kg LPS for five days. Clinical scores were graded at 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. The concentrations of IL-17, INF-γ, and IL-6 in aqueous humor were quantified with enzyme-linked immunosorbent assay. Real-time PCR, Western blot, and immunofluorescence analysis were used to determine the expression of NF-κB P65 and the activation of CSF-1, LRR-1. Results: Low dose of LPS pretreatment produced a suppressive effect by significantly reducing the inflammatory reaction of anterior segment as measured by slit lamp and histopathology. It also significantly reduced the concentrations of IL-17, INF-γ, and IL-6 in aqueous humor and the expression of CSF-1 and NF-κB P65, while increased the expression of LRR-1 compared to the EIU group. Conclusions. Low dose of LPS pretreatment can ameliorate endotoxin-induced uveitis in rats. This protection may be associated with upregulation of LRR-1 and downregulation of CSF-1, which is regulated by TLR4 signaling pathway.

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Protection of Lipopolysaccharide (LPS) Preconditioning against Endotoxin-Induced Uveitis (EIU) in Rats is Associated with Overexpression of Interleukin-1 Receptor-Associated Kinase M (IRAK-M)

Abstract: Endotoxin tolerance has a protective effect against EIU, and upregulation of IRAK-M through TLR-signaling pathway is one of the most likely candidates to be involved in the observed phenomenon.

Cited by 8 publications

References 23 publications

A systematic review and meta-analyses of interleukin-1 receptor associated kinase 3 (IRAK3) action on inflammation in in vivo models for the study of sepsis

A systematic review and meta-analyses of interleukin-1 receptor associated kinase 3 (IRAK3) action on inflammation in in vivo models for the study of sepsis

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

The Protective Effect of Low Dose of Lipopolysaccharide Pretreatment on Endotoxin-Induced Uveitis in Rats Is Associated with Downregulation of CSF-1 and Upregulation of LRR-1

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