| 61. |
- Luo, Zhengkang, et al.
(författare)
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Kinetics of immune cell responses in the multiple low dose streptozotocin mouse model of type 1 diabetes
- 2019
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Ingår i: FASEB BioAdvances. - : Wiley. - 2573-9832. ; 1, s. 538-549
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In type 1 diabetes (T1D), the insulin-producing β cells are destructed by immune mechanisms. It has been hypothesized that the very first immune response in T1D onset comes from innate immune cells, which further activates the adaptive immune cells to attack the islets. Despite intensive research on characterization of islet-infiltrating immune cells, the kinetics of different immune cells in multiple low-dose streptozotocin (MLDSTZ)-induced T1D mouse model is still much unclear. Therefore, we investigated the proportions of innate immune cells such as neutrophils, dendritic cells (DCs), plasmacytoid dendritic cells (pDCs), macrophages, natural killer (NK) cells, and adaptive immune cells (T and B lymphocytes) in thymi, pancreatic-draining lymph nodes, and spleens of MLDSTZ mice on days 3, 7, 10, and 21 after the first injection of STZ by flow cytometry. The proportions of DCs and B cells were increased from day 3, while the proportions of B-1a lymphocytes and interferon-γ+ cells among NK cells were increased, but NK cells were decreased on day 10 in MLDSTZ-treated mice, illustrating that the initial immune response is induced by DCs and B cells. Later, the proportions of T helper 1 and cytotoxic T cells were increased from day 7, suggesting that the innate immune cells precede adaptive immune cell response in MLDSTZ mice. Altogether, our data demonstrate a possible sequence of events regarding the involvement of DCs, pDCs, NK cells, B-1a lymphocytes, B, and T cells at the early stage of T1D development.
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| 62. |
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| 63. |
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| 64. |
- Martinell, Mats, 1971-, et al.
(författare)
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Characterization of Cellular Immunology in LADA Patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Patients with latent autoimmune diabetes mellitus in adults (LADA) have antibodies against the insulin-producing b-cells but at disease onset they are not insulin-dependent. This study presents cellular immunological differences between LADA, type 1, type 2 diabetes and healthy controls.Research Design and Methods: All patients and matched (by age, gender and body mass index) healthy controls were recruited from the County of Uppsala, Sweden. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine proportions of innate, adaptive and regulatory immune cells by using flow cytometry. Results: Included were 14 patients with LADA, 16 with type 1 diabetes, 16 with type 2 diabetes and 13 healthy controls. The proportion of CD11c+CD123- antigen presenting cells (APCs) was lower, whilst proportions of CD11c+CD123+ APCs and Interleukin (IL)-35+ tolerogenic APCs were higher in LADA patients compared to patients with type 1 diabetes. The proportion of CD3-CD56highCD16+ Natural Killer (NK) cells was higher in LADA patients than in both healthy controls and type 2 diabetes patients. IL-35+ Treg cell numbers were similar to those observed in both type 1 diabetes and type 2 diabetes patients, but a lower frequency of IL-35+ regulatory T (Treg) cells was observed in LADA patients than in healthy controls. The proportion of regulatory B (Breg) cells in LADA patients was higher than in healthy controls, type 1 and type 2 diabetes patients and IL-35+ Breg cell numbers were higher than in type 1 diabetes patients. Conclusions: LADA patients present a mixed cellular immunological pattern compared to type 1 and type 2 diabetes patients. Numbers of APCs, IL-35+ tolerogenic APCs and IL-35+ Breg cells in LADA patients are similar to those observed in type 2 diabetes patients, whereas the changes in NK cells are similar to those observed in type 1 diabetes patients.
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| 65. |
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| 66. |
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| 67. |
- Niklasson, Bo, et al.
(författare)
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Prenatal viral exposure followed by adult stress produces glucose intolerance in a mouse model
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:9, s. 2192-2199
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: It has been suggested that the uterine environment may influence metabolic disease occurring later in adult life, and that adult stress may promote disease outcome. Using a mouse model, we tested whether in utero exposure to Ljungan virus (LV) followed by adult exposure to stress produces diabetes. The influence of the timing of viral exposure over the course of pregnancy was also tested. Materials and methods: Pregnant CD-1 mice were exposed i.p. to LV on pregnancy days 4, 8, 12 or 17. Adult male mice from these pregnancies were stressed by being kept in shared cages. Stress only, LV exposure in utero only, and no-stress/no virus exposure groups were also followed. Outcome variables included bodyweight, epididymal fat weight, baseline glucose, glucose tolerance tests (60 and 120 min) and serum insulin. Results: We demonstrated that male mice developed a type 2-like diabetes, including obesity, as adults if infected during pregnancy with LV. Diabetes at the age of 11 weeks was more severe in mice whose mothers were infected earlier than in those whose mothers were infected later in pregnancy. Only animals infected in utero and kept under stress developed diabetes; infection or stress alone did not cause disease. Conclusions/interpretation: This work demonstrates that a type 2 diabetes-like disease can be virus-induced in a mouse model. Early in utero viral insults can set the stage for disease occurring during adult life, but the final manifestation of diabetes is dependent on the combination of early viral exposure and stress in adult life.
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| 68. |
- Phillipson, Mia, et al.
(författare)
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Inducible nitric oxide synthase is involved in acid-induced gastric hyperemia in rats and mice
- 2003
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Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 285:1, s. G154-G162
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Tidskriftsartikel (refereegranskat)abstract
- The role of different isoforms of nitric oxide synthase (NOS) in the gastric mucosal hyperemia, induced by 155 mM luminal hydrochloric acid (pH approximately 0.8) without a barrier breaker, was investigated. Rats were anesthetized with Inactin (120 mg/kg ip), and mice were anesthetized with Forene (2.2% in 40% oxygen gas at 150 ml/min); the gastric mucosa was exteriorized. Gastric mucosal blood flow was measured with laser-Doppler flowmetry (LDF) in rats treated with Nomega-nitro-l-arginine (l-NNA; unspecific NOS inhibitor), l-N6-(1-iminoethyl)lysine [l-NIL; inducible (i) NOS inhibitor], or S-methyl-l-thiocitrulline [SMTC; neuronal (n) NOS inhibitor], 10 mg/kg, followed by 3 mg. kg-1. h-1 iv, in iNOS-deficient (-/-) and nNOS(-/-) mice. mRNA was isolated from the gastric mucosa in iNOS(-/-) and wild-type (wt) mice, and real-time RT-PCR was performed. The effect of 155 mM acid on gastric mucosal permeability was determined by measuring the clearance of 51Cr-EDTA from blood to lumen. LDF increased by 48 +/- 13% during 155 mM HCl luminally, an increase that was abolished by l-NNA, SMTC, or l-NIL. In iNOS wt mice, LDF increased by 33 +/- 8% during luminal acid. The blood flow increase was attenuated substantially in iNOS(-/-) mice. RT-PCR revealed iNOS mRNA expression in the gastric mucosa in the iNOS wt groups. The blood flow increase in response to acid was not abolished in nNOS(-/-) mice (nNOS-sufficient mice, 39 +/- 18%; heterozygous mice, 25 +/- 19%; -/- mice, 19 +/- 7%). Mucosal permeability was transiently increased during 155 mM HCl. The results suggest that iNOS is constitutively expressed in the gastric mucosa and is involved in acid-induced hyperemia, suggesting a novel role for iNOS in gastric mucosal protection.
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| 69. |
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| 70. |
- Phillipson, Mia, et al.
(författare)
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The gastric mucus layers: constituents and regulation of accumulation.
- 2008
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 295:4
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Tidskriftsartikel (refereegranskat)abstract
- The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1-/-, inducible nitric oxide synthase (iNOS)-/-, and neuronal NOS (nNOS)-/-] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE(2) increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1-/- mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE(2) and NO. A new gastroprotective role for iNOS was indicated since iNOS-/- mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1-/- mice.
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