Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain

Zhang, Hao; Ching, San; Chen, Qun; Li, Qiming; An, Ying; Quan, Ning

doi:10.1016/j.neuroscience.2008.09.038

Cited by 31 publications

(33 citation statements)

References 56 publications

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“…A further study in mice provides evidence for hippocampusdependent learning and memory impairment after LPS injection (30). Systemic administration of LPS is reported to induce TLR4-dependent secretion of proinflammatory cytokines such as IL-1b, IL-6, and TNF in the CNS (31)(32)(33)(34). Furthermore, activation of TLR4 by LPS increases IFN-g levels in mice and stimulates IDO in peripheral tissues and the brain (35).…”

Section: Discussionmentioning

confidence: 95%

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Vollmar

Kullmann

Thilo

et al. 2010

The Journal of Immunology

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Active immunization with amyloid-β (Aβ) peptide 1–42 reverses amyloid plaque deposition in the CNS of patients with Alzheimer’s disease and in amyloid precursor protein transgenic mice. However, this treatment may also cause severe, life-threatening meningoencephalitis. Physiological responses to immunization with Aβ1–42 are poorly understood. In this study, we characterized cognitive and immunological consequences of Aβ1–42/CFA immunization in C57BL/6 mice. In contrast to mice immunized with myelin oligodendrocyte glycoprotein (MOG)35–55/CFA or CFA alone, Aβ1–42/CFA immunization resulted in impaired exploratory activity, habituation learning, and spatial-learning abilities in the open field. As morphological substrate of this neurocognitive phenotype, we identified a disseminated, nonfocal immune cell infiltrate in the CNS of Aβ1–42/CFA-immunized animals. In contrast to MOG35–55/CFA and PBS/CFA controls, the majority of infiltrating cells in Aβ1–42/CFA-immunized mice were CD11b+CD14+ and CD45high, indicating their blood-borne monocyte/macrophage origin. Immunization with Aβ1–42/CFA was significantly more potent than immunization with MOG35–55/CFA or CFA alone in activating macrophages in the secondary lymphoid compartment and peripheral tissues. Studies with TLR2/4-deficient mice revealed that the TLR2/4 pathway mediated the Aβ1–42-dependent proinflammatory cytokine release from cells of the innate immune system. In line with this, TLR2/4 knockout mice were protected from cognitive impairment upon immunization with Aβ1–42/CFA. Thus, this study identifies adjuvant effects of Aβ1–42, which result in a clinically relevant neurocognitive phenotype highlighting potential risks of Aβ immunotherapy.

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Section: Discussionmentioning

confidence: 95%

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Vollmar

Kullmann

Thilo

et al. 2010

The Journal of Immunology

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show abstract

“…Briefly, the cells were incubated with 10 Ϫ6 M of Dex or vehicle overnight and then washed with culture medium three times before IL-1␣ (final concentration of IL-1␣ in the cultures was 1 ng/ml) was added to the cultures. RNA was extracted from these cultured cells 2 h later and analyzed for the expression of cyclooxygenase 2 (COX-2) mRNA levels using quantitative RT-PCR as we described previously (14).…”

Section: Methodsmentioning

confidence: 99%

Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I

Chen

Zhang

et al. 2009

Journal of Biological Chemistry

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The type 1 interleukin-1 receptor (IL-1R1) mediates diverse functions of interleukin-1 (IL-1) in the nervous, immune, and neuroendocrine systems. It has been suggested previously that the versatile functions of IL-1 may in part be conferred by the multiple promoters of IL-1R1 that have been identified for the human IL-1R1 gene. Promoters for murine IL-1R1 (mIL-1R1) gene have not been studied in detail. We performed 5-rapid amplification of cDNA ends to determine the transcription start sites (TSS) in mIL-1R1, using mRNAs derived from 24 different tissues. The results revealed three putative TSSs of mIL-1R1. Three full-length cDNAs containing these distinct TSSs were recovered in screens of cloned cDNA libraries. Translation of these cDNAs produced IL-1R1 proteins that were verified by Western blot analysis. IL-1 stimulation of the individual IL-1R1 proteins resulted in the activation of NF-B. Promoter-reporter assay for genomic DNA sequences immediately upstream of the three TSSs validated that the sequences possess promoter activity in a cell type-specific manner. These promoters are termed P1, P2, and P3 of the mIL-1R1, in 5 to 3 order. Quantitative PCR analysis of P1-, P2-, and P3-specific mIL-1R1 mRNAs showed that there is tissue-specific distribution of these mRNAs in vivo, and there are distinct patterns of P1, P2, and P3 mRNA expression in different cell lines. In the brain, P3 mRNA is expressed preferentially in the dentate gyrus. Further, glucocorticoids differentially regulate these promoters in a cell type-specific manner. Together, these results suggest that the different IL-1R1 promoters contribute to the discrete and diverse actions of IL-1.

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“…This has been used in many studies of atherosclerosis and liver steatosis (Miura et al 1985, Wal 2002, Ma et al 2008. In comparison with other sole cytokine or lipopolysaccharide (LPS)-induced mouse models, casein injection induces a lower degree inflammatory stress characterized by increased multiple cytokines (IL1b, TNFa, and IL6) and SAA (like CRP in human) levels in serum, which is more likely to mimic chronic systemic inflammatory state observed in patients with inflammatory stress (Zhang et al 2008). The current study was undertaken to investigate whether chronic inflammation induced by casein injection exacerbated pancreatic b cell dysfunction resulting in hyperglycemia in high-fat diet (HFD)-fed C57BL/6J mice and to explore its underlying mechanism.…”

Section: Introductionmentioning

confidence: 99%

Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet

Wu¹,

Wu²,

Wu³

et al. 2013

Journal of Endocrinology

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Inflammatory stress is closely related to metabolic disease and insulin resistance. The precise cellular mechanism linking obesity and diabetes is largely unknown, but about 14-20% of obese individuals develop diabetes. In this study, we investigated whether chronic inflammation exacerbated glucose metabolism disorder by impairing b cell function in high-fat diet (HFD)-fed C57BL/6J mice. We used s.c. casein injection to induce chronic inflammation in HFD-fed C57BL/6J mice; 14 weeks on a HFD resulted in weight gain, hyperlipidemia, and low insulin sensitivity in these mice which nevertheless had normal blood glucose and serum inflammatory cytokines levels. Casein injection in the background of HFD elevated serum tumor necrosis factor a (TNFa) and serum amyloid A levels and increased TNFa and MCP1 expression in the adipose tissue, liver, and muscle of HFD-fed mice. Chronic inflammation induced by casein injection further decreased insulin sensitivity and insulin signaling, resulting in insulin deficiency and hyperglycemia in these mice. Islet mass and insulin content were markedly increased in HFD mice. However, in contrast with HFD-fed alone, chronic inflammation in HFD-fed mice decreased both islet mass and insulin content, reduced the genetic expression of insulin synthesis and secretion, and increased b cell apoptosis. We conclude that chronic inflammation exacerbated glucose metabolism disorders by impairing b cell function in HFD-fed C57BL/6J mice, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to hyperglycemia. Key Words" glucose metabolism " inflammatory diseases " insulin " apoptosis " pancreas

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Localized inflammation in peripheral tissue signals the CNS for sickness response in the absence of interleukin-1 and cyclooxygenase-2 in the blood and brain

Cited by 31 publications

References 56 publications

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Active Immunization with Amyloid-β 1–42 Impairs Memory Performance through TLR2/4-Dependent Activation of the Innate Immune System

Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I

Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet

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