| 1. |
- Ahl, David, et al.
(författare)
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Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice
- 2016
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 217:4, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study was to investigate whether two Lactobacillus reuteri strains (rat-derived R2LC and human-derived ATCC PTA 4659 (4659)) could protect mice against colitis, as well as delineate the mechanisms behind this protection.Methods: Mice were given L.reuteri R2LC or 4659 by gavage once daily for 14days, and colitis was induced by addition of 3% DSS (dextran sulphate sodium) to drinking water for the last 7days of this period. The severity of disease was assessed through clinical observations, histological evaluation and ELISA measurements of myeloperoxidase (MPO) and pro-inflammatory cytokines from colonic samples. Mucus thickness was measured invivo with micropipettes, and tight junction protein expression was assessed using immunohistochemistry.Results: Colitis severity was significantly reduced by L.reuteri R2LC or 4659 when evaluated both clinically and histologically. The inflammation markers MPO, IL-1, IL-6 and mKC (mouse keratinocyte chemoattractant) were increased by DSS and significantly reduced by the L.reuteri strains. The firmly adherent mucus thickness was reduced by DSS, but significantly increased by L.reuteri in both control and DSS-treated mice. Expression of the tight junction proteins occludin and ZO-1 was significantly increased in the bottom of the colonic crypts by L.reuteri R2LC.Conclusion: These results demonstrate that each of the two different L. reuteri strains, one human-derived and one-rat-derived, protects against colitis in mice. Mechanisms behind this protection could at least partly be explained by the increased mucus thickness as well as a tightened epithelium in the stem cell area of the crypts.
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| 2. |
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| 3. |
- Anderberg, Sara B., et al.
(författare)
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Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury
- 2017
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Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 219:3, s. 575-590
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Forskningsöversikt (refereegranskat)abstract
- Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram-negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI-AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI-AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI-AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI-AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.
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| 4. |
- Barragan, Antonio, et al.
(författare)
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GABAergic signalling in the immune system
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 213:4, s. 819-827
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Forskningsöversikt (refereegranskat)abstract
- The GABAergic system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates. Signalling of the transmitter c-aminobutyric acid (GABA) via GABA type A receptor channels or G-protein-coupled type B receptors is implicated in multiple CNS functions. Recent findings have implicated the GABAergic system in immune cell functions, inflammatory conditions and diseases in peripheral tissues. Interestingly, the specific effects may vary between immune cell types, with stage of activation and be altered by infectious agents. GABA/GABA-A receptor-mediated immunomodulatory functions have been unveiled in immune cells, being present in T lymphocytes and regulating the migration of Toxoplasma-infected dendritic cells. The GABAergic system may also play a role in the regulation of brain resident immune cells, the microglial cells. Activation of microglia appears to regulate the function of GABAergic neurotransmission in neighbouring neurones through changes induced by secretion of brain-derived neurotrophic factor. The neurotransmitter-driven immunomodulation is a new but rapidly growing field of science. Herein, we review the present knowledge of the GABA signalling in immune cells of the periphery and the CNS and raise questions for future research.
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| 5. |
- Bhandage, Amol K., 1988-, et al.
(författare)
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Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 213:3, s. 575-585
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Tidskriftsartikel (refereegranskat)abstract
- AimThe concept of nerve-driven immunity recognizes a link between the nervous and the immune system. -aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain, and receptors activated by GABA can be expressed by immune cells. Here, we examined whether the expression of GABA receptors and chloride transporters in human peripheral blood mononuclear cells (PBMCs) was influenced by gender, pregnancy or mental health. MethodsWe used RT-qPCR to determine the mRNA expression level in PBMCs from men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15). ResultsThe 2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The and 2 subunits were up-regulated by pregnancy, whereas the epsilon subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in turn, commonly expressed the 6 and the 2 subunits. The 1 and epsilon subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women, while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs. ConclusionThe results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.
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| 7. |
- Bhattachariya, Anirban, et al.
(författare)
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Spontaneous activity and stretch-induced contractile differentiation are reduced in vascular smooth muscle of miR-143/145 knockout mice.
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 215:3, s. 133-143
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Tidskriftsartikel (refereegranskat)abstract
- Stretch is essential for maintaining the contractile phenotype of vascular smooth muscle cells, and small non-coding microRNAs are known to be important in this process. Using a Dicer knockout model, we have previously reported that microRNAs are essential for stretch-induced differentiation and regulation of L-type calcium channel expression. The aim of this study was to investigate the importance of the smooth muscle-enriched miR-143/145 microRNA cluster for stretch-induced differentiation of the portal vein.
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| 8. |
- Birnir, Bryndis, et al.
(författare)
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She is in science to stay!
- 2018
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Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 223:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Bjarnegård, Niclas, 1964-, et al.
(författare)
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Vascular characteristics in young women-Effect of extensive endurance training or a sedentary lifestyle
- 2018
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 223:2
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore whether high-level endurance training in early age has an influence on the arterial wall properties in young women. Methods: Forty-seven athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further divided into runners (RUN), whole-body endurance athletes (WBA), sedentary controls (SC) and normally active controls (AC). Two-dimensional ultrasound scanning of the carotid arteries was conducted to determine local common carotid artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a tonometer to determine regional pulse wave velocity (PWV) and pulse pressure waveform. Results: Carotid-radial PWV was lower in WBA than in RUN (P < .05), indicating higher arterial distensibility along the arm. Mean arterial pressure was lower in ATH than in CTR and in RUN than in WBA (P < .05). Synthesized aortic augmentation index (AI at 75) was lower among ATH than among CTR (-12.8 ± 1.6 vs -2.6 ± 1.2%, P < .001) and in WBA than in RUN (-16.4 ± 2.5 vs -10.7 ± 2.0%, P < .05), suggesting a diminished return of reflection waves to the aorta during systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and radial distensibility of the CCA were similar in ATH and CTR. Conclusion: Elastic artery distensibility and carotid artery IMT are not different in young women with extensive endurance training over several years and in those with sedentary lifestyle. On the other hand, our data suggest that long-term endurance training is associated with potentially favourable peripheral artery adaptation, especially in sports where upper body work is added. This adaptation, if persisting later in life, could contribute to lower cardiovascular risk.
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| 10. |
- Blanchard, P. G., et al.
(författare)
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Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes
- 2016
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 217:3, s. 227-239
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood.Methods: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg−1 day−1, 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding.Results: Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF.Conclusions: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.
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