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Sökning: WFRF:(Wikstrom AC)

  • Resultat 1-48 av 48
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  • Georen, SK, et al. (författare)
  • Timing-dependent effects of restraint stress on eosinophilic airway inflammation in mice
  • 2008
  • Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 15:3, s. 157-164
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Chronicstress has been proposed to aggravate allergic inflammation, whereas acute stress may have functional beneficial effects. The aim of this study was to investigate the influence of timing of single short restraint stress (RST) in a model of eosinophilic airway inflammation. <i>Methods:</i> The airways of ovalbumin (OVA)-sensitized mice were exposed to an intranasal OVA challenge. RST was applied in two different ways; either 2 h before (pre-stress) or after (post-stress) the OVA challenge, respectively, or as a combination of stress before and after (double-stress) the OVA challenge. One group of mice was also treated with metyrapone (ME) prior to a pre-stress challenge. The inflammatory cell response was evaluated in bronchoalveolar lavage fluid (BALF), lung and nasal tissue, as well as bone marrow. <i>Result:</i> RST applied prior to the OVA challenge (pre-stress) inhibited OVA-induced airway inflammation in BALF and lung tissue, and reduced nasal histopathology compared to unstressed mice. Given as post-stress or double-stress, RST did not affect the inflammation in BALF, lungs or nasal tissue. Pre-treatment with ME prevented the pre-challenge stress evoked decrease in inflammation in BALF and lungs. <i>Conclusion:</i> Effects of RST on eosinophilic airway inflammation appear to be strongly dependent on timing and, as could be judged from the ME inhibition pattern, also corticosterone dependent. Hypothalamic-pituitary-adrenal axis activation probably influences eosinophilic inflammation through specific sequences of compartmental activation and thereby timing effects are evident on cellular recruitment pattern during the allergic reaction.
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  • Lekander, M, et al. (författare)
  • Cytokine inhibition after glucocorticoid exposure in healthy men with low versus high basal cortisol levels
  • 2009
  • Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 16:4, s. 245-250
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Objective:</i> The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. <i>Methods:</i>136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m<sup>2</sup>) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. <i>Results:</i>After exposure to DEX in vivo<i>,</i> inhibition of IL-6 and TNF-α decreased. Also<i>, </i>after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. <i>Conclusion:</i> A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.
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  • Sun, ND, et al. (författare)
  • Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing
  • 2018
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 17509-
  • Tidskriftsartikel (refereegranskat)abstract
    • Capable of mediating efficient transfection and protein production without eliciting innate immune responses, chemically modified mRNA holds great potential to produce paracrine factors at a physiologically beneficial level, in a spatiotemporally controlled manner, and with low toxicity. Although highly promising in cardiovascular medicine and wound healing, effects of this emerging therapeutic on the microvasculature and its bioactivity in disease settings remain poorly understood. Here, we longitudinally and comprehensively characterize microvascular responses to AZD8601, a modified mRNA encoding vascular endothelial growth factor A (VEGF-A), in vivo. Using multi-parametric photoacoustic microscopy, we show that intradermal injection of AZD8601 formulated in a biocompatible vehicle results in pronounced, sustained and dose-dependent vasodilation, blood flow upregulation, and neovessel formation, in striking contrast to those induced by recombinant human VEGF-A protein, a non-translatable variant of AZD8601, and citrate/saline vehicle. Moreover, we evaluate the bioactivity of AZD8601 in a mouse model of diabetic wound healing in vivo. Using a boron nanoparticle-based tissue oxygen sensor, we show that sequential dosing of AZD8601 improves vascularization and tissue oxygenation of the wound bed, leading to accelerated re-epithelialization during the early phase of diabetic wound healing.
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  • TEBOUL, M, et al. (författare)
  • OR-1, a member of the nuclear receptor superfamily that interacts with the 9-cis-retinoic acid receptor
  • 1995
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:6, s. 2096-2100
  • Tidskriftsartikel (refereegranskat)abstract
    • We have cloned a member of the nuclear receptor superfamily. The cDNA was isolated from a rat liver library and encodes a protein of 446 aa with a predicted mass of 50 kDa. This clone (OR-1) shows no striking homology to any known member of the steroid/thyroid hormone receptor superfamily. The most related receptor is the ecdysone receptor and the highest homologies represent < 10% in the amino-terminal domain, between 15-37% in the carboxyl-terminal domain and 50-62% in the DNA binding domain. The expression of OR-1 appears to be widespread in both fetal and adult rat tissues. Potential DNA response elements composed of a direct repeat of the hexameric motif AGGTCA spaced by 0-6 nt were tested in gel shift experiments. OR-1 was shown to interact with the 9-cis-retinoic acid receptor (retinoid X receptor, RXR) and the OR-1/RXR complex to bind to a direct repeat spaced by 4 nt (DR4). In transfection experiments, OR-1 appears to activate RXR-mediated function through the DR4. Therefore OR-1 might modulate 9-cis-retinoic acid signaling by interacting with RXR.
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  • Wikstrom, AC (författare)
  • Glucocorticoid action and novel mechanisms of steroid resistance: role of glucocorticoid receptor-interacting proteins for glucocorticoid responsiveness
  • 2003
  • Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 178:3, s. 331-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucocorticoids are widely used to treat inflammatory and malignant diseases. However, many individuals show a lack of therapeutic response and unwanted side-effects. Various known and unknown parameters determine glucocorticoid responsiveness, among them glucocorticoid receptor (GR)-interacting proteins. Several of the proteins interacting with GR also participate in other signal transduction pathways such as the AP-1 pathway and the nuclear factor-kappaB pathway. We suggest that a closer study of GR-interacting proteins may shed new light on mechanisms determining glucocorticoid sensitivity. In this commentary, the general mechanisms of GR action will be addressed and a proteomic-based method to study GR-interacting proteins will be described in brief.
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  • Resultat 1-48 av 48

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