| 31. |
- Persson, Carl, et al.
(författare)
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The mouse trap
- 1997
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Ingår i: Trends in Pharmacological Sciences. - 0165-6147. ; 18:12, s. 465-467
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Tidskriftsartikel (refereegranskat)abstract
- Mouse models of asthma are now being used extensively in drug research. However, the successful unravelling of combinatorial interplays of cells and molecules in the murine airways may not be matched by equally successful demonstrations of an asthma-like pathophysiology. Here, Carl Persson, Jonas Erjefalt, Magnus Korsgren and Frank Sundler discuss the fact that major features of asthma may still need to be demonstrated in the airways of allergic mice.
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| 32. |
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| 33. |
- Amoudruz, Petra, et al.
(författare)
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Maternal country of birth and previous pregnancies are associated with breast milk characteristics
- 2009
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 20:1, s. 19-29
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Tidskriftsartikel (refereegranskat)abstract
- Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn’s disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-β1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.
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| 34. |
- Boij, Roland, 1952-
(författare)
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Aspects of inflammation, angiogenesis and coagulation in preeclampsia
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia is a major challenge to obstetricians, due to its impact on maternal and fetal morbidity and mortality and the lack of preventive and treatment strategies. The overall aim of this thesis is to increase the knowledge of the pathogenesis of preeclampsia including the role of inflammation, angiogenesis and coagulation, both locally at the fetomaternal interface and in the maternal circulation. Uncompensated maternal endothelial inflammatory responses to factors from stressed trophoblasts seem to be a major contributor to the syndrome, together with an imbalance in angiogenesis and an activated coagulation system. An increasing amount of data indicates an involvement of the immune system with defect tolerance to the conceptus as an integral part of the pathogenesis, at least in early-onset preeclampsia (EOP).We showed that a single administration of human preeclampsia serum in pregnant IL-10−/− mice induced the full spectrum of preeclampsia-like symptoms including hypoxic injury in uteroplacental tissues and endotheliosis in maternal kidneys. Importantly, preeclampsia serum, as early as 12 to 14 weeks of gestation, disrupted cross talk between trophoblasts and endothelial cells in an in vitro model of endovascular activity (Tube formation test). These results indicate that preeclamptic sera can be used to better understand the pathophysiology and to predict the disorder. Preeclampsia has been associated with increased inflammation, aberrant angiogenesis and activated coagulation, but their correlation and relative contribution are unknown. We found that markers for all these mechanisms were independently associated with preeclampsia. Cytokines, chemokines, and complement factors seem all to be part of a Th1-associated inflammatory reaction in preeclampsia, more pronounced in EOP than in late-onset preeclampsia (LOP), in line with a more homogeneous pathogenesis in EOP as based on placental pathology. In women with intrauterine growth restriction (IUGR), with an anticipated pathologic placentation, only differences in levels for sFlt-1 and PlGF were found in comparison with mothers without IUGR. Thus, sFlt-1 and PlGF seem to be indicators of placental pathology, while other biomarkers might also reflect maternal endothelial pathology. Chemokines, in contrast to cytokines, may prove to be useful markers in preeclampsia.A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Utilizing recent advances in flow cytometry phenotyping, we found no major alterations in circulating Treg numbers in preeclamptic women compared with normal pregnant and non-pregnant women. However, preeclampsia was associated with increased fractions of CTLA-4+ and CCR4+ cells within Treg subpopulations, which is in line with a migratory defect of Treg cells, and potentially associated with a reduced number of suppressive Treg cells at the fetomaternal interface. As we found that corticosteroid treatment affected the results, it should be accounted for in studies of EOP. Chemokines are supposed to be part of the immune adaptation in pregnancy. We found a decreased expression of CCL18 (Th2/Tregassociated), in trophoblasts from preeclamptic compared to normal pregnant women, indicating a local regulatory defect in preeclampsia, in line with our finding of a possible migratory defect of circulating Treg cells. Due to increased expression of CCL20 (Th17) and CCL22 (Th2) in first trimester placenta and increased circulating levels of CXCL10 (Th1) and CCL20 (Th17) in third trimester preeclamptic women, we suggest that CCL20 and CCL22 may be important for implantation and early placentation while in third trimester of a preeclamptic pregnancy CXCL10 and CCL20 mainly mirror maternal increased endothelial inflammation and aberrant angiogenesis. In summary, we found that preeclampsia is associated with increased inflammation, aberrant angiogenesis and activated coagulation, caused by placental factors in maternal peripheral circulation, more pronounced in the early-onset form of preeclampsia. It also appears that there is a defective modulation of the immune system in preeclamptic pregnancies. The results provide a better understanding of the pathogenesis of preeclampsia and have given suggestions to predictive markers for preeclampsia in the future.
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| 35. |
- Gustafsson, Lars, et al.
(författare)
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Infectious disease, reproductive effort and the cost of reproduction in birds
- 1994
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Ingår i: Philosophical transactions of the Royal Society of London: Series B. ; :346, s. 1655-1658
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Reproductive effort can have profound effects on subsequent performance. Field experiments on the collared flycatcher (Ficedula albicollis) have demonstrated a number of trade-offs between life-history traits at different ages. The mechanism by which reproductive effort is mediated into future reproductive performance remains obscure. Anti-parasite adaptations such as cell-mediated immunity may probably also be costly. Hence the possibility exists of a trade-off between reproductive effort and the ability to resist parasitic infection. Serological tests on unmanipulated collared flycatchers show that pre-breeding nutritional status correlates positively with reproductive success and negatively with susceptibility to parasitism (viruses, bacteria and protozoan parasites). Both immune response and several indicators of infectious disease correlate negatively with reproductive success. Similar relations are found between secondary sexual characters and infection parameters. For brood-size-manipulated birds there was a significant interaction between experimentally increased reproductive effort and parasitic infection rate with regard to both current and future fecundity. It seems possible that the interaction between parasitic infection, nutrition and reproductive effort can be an important mechanism in the ultimate shaping of life-history variation in avian populations.
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| 36. |
- Johansson, Martin L, et al.
(författare)
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Multimodal Analysis of the Tissue Response to a Bone-Anchored Hearing Implant: Presentation of a Two-Year Case Report of a Patient With Recurrent Pain, Inflammation, and Infection, Including a Systematic Literature Review.
- 2021
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Osseointegration is a well-established concept used in applications including the percutaneous Bone-Anchored Hearing System (BAHS) and auricular rehabilitation. To date, few retrieved implants have been described. A systematic review including cases where percutaneous bone-anchored implants inserted in the temporal bone were retrieved and analyzed was performed. We also present the case of a patient who received a BAHS for mixed hearing loss. After the initial surgery, several episodes of soft tissue inflammation accompanied by pain were observed, leading to elective abutment removal 14 months post-surgery. Two years post-implantation, the implant was removed due to pain and subjected to a multiscale and multimodal analysis: microbial DNA using molecular fingerprinting, gene expression using quantitative real-time polymerase chain reaction (qPCR), X-ray microcomputed tomography (micro-CT), histology, histomorphometry, backscattered scanning electron microscopy (BSE-SEM), Raman spectroscopy, and fluorescence in situ hybridization (FISH). Evidence of osseointegration was provided via micro-CT, histology, BSE-SEM, and Raman spectroscopy. Polymicrobial colonization in the periabutment area and on the implant, including that with Staphylococcus aureus and Staphylococcus epidermidis, was determined using a molecular analysis via a 16S-23S rDNA interspace [IS]-region-based profiling method (IS-Pro). The histology suggested bacterial colonization in the skin and in the peri-implant bone. FISH confirmed the localization of S. aureus and coagulase-negative staphylococci in the skin. Ten articles (54 implants, 47 patients) met the inclusion criteria for the literature search. The analyzed samples were either BAHS (35 implants) or bone-anchored aural epitheses (19 implants) in situ between 2 weeks and 8years. Themainreasons for elective removal were nonuse/changes in treatment, pain, or skin reactions. Most samples were evaluated using histology, demonstrating osseointegration, but with the absence of bone under the implants' proximal flange. Taken together, the literature and this case report show clear evidence of osseointegration, despite prominent complications. Nevertheless, despite implant osseointegration, chronic pain related to the BAHS may be associated with a chronic bacterial infection and raised inflammatory response in the absence of macroscopic signs of infection. It is suggested that a multimodal analysis of peri-implant health provides possibilities for device improvements and to guide diagnostic and therapeutic strategies to alleviate the impact of complications.
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| 37. |
- Svensson, Andreas
(författare)
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Mesenchymal stromal cells in malignant glioma - Functions and therapeutic potential
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The most common malignant brain tumor in adults is a glioma called glioblastoma multiforme (GBM). About 300 persons are diagnosed with GBM every year in Sweden. Unfortunately, it is also the most aggressive brain tumor and as of today, it is not possible to cure it. Despite treating the patients with surgery, radiation and chemotherapy, the median survival is only 15 months. The main problem with GBM is its infiltrative growth. As the tumor cells leave the tumor bulk and migrate into the normal brain parenchyma, it is impossible to reach them with the current standard treatments. Hence, even after treatment, some tumor cells will remain in the brain and eventually give rise to a new tumor. To be able to reach the migrating cells, new treatment strategies need to be developed. One such strategy is to use stem cells as drug delivery vehicles. It has been shown that mesenchymal stromal cells (MSCs) derived from the bone marrow (BM) have the ability to specifically migrate throughout a glioma. Upon intratumoral transplantation, they spread within the tumor, along its extensions and toward migrating tumor cells that has left the main tumor bulk, making BM-MSCs ideal as transporters of anti-tumoral substances. However, several safety concerns have been raised as MSCs also have shown to mediate tumor growth by acting immunosuppressive and contribute to the tumor stroma and vascularization. This thesis will discuss 1) the role of endogenous MSCs in malignant glioma and 2) the use of transplanted BM-MSCs as glioma treatment. We have shown that human malignant gliomas harbor two distinct cell populations that resemble BM-MSCs. We have characterized the cells and conclude that they most likely play an important role in tumor angiogenesis and immunosuppression. Further on, we have seen that MSC-like pericytes within the normal mouse brain are activated by, and migrate into, an orthotopic glioma model. The cells align perivascularly and contribute the majority of all pericytes within the tumor. To evaluate their tumor-tropism, MSCs were derived from rat bone marrow and transplanted into, and adjacent to, orthotopic rat gliomas. We conclude that even though they show strong tumor-tropic migration capabilities upon intratumoral transplantation they do not migrate when transplanted into the normal brain of tumor bearing animals. We also report that intratumorally transplanted BM-MSCs potentiate the effect of peripheral immunotherapy against malignant gliomas, demonstrating their use in a therapeutic setting.
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| 38. |
- Khoomrung, Sakda, 1978, et al.
(författare)
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Metabolic Profiling and Compound-Class Identification Reveal Alterations in Serum Triglyceride Levels in Mice Immunized with Human Vaccine Adjuvant Alum
- 2020
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 19:1, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- Alum has been widely used as an adjuvant for human vaccines; however, the impact of Alum on host metabolism remains largely unknown. Herein, we applied mass spectrometry (MS) (liquid chromatography-MS)-based metabolic and lipid profiling to monitor the effects of the Alum adjuvant on mouse serum at 6, 24, 72, and 168 h post-vaccination. We propose a new strategy termed subclass identification and annotation for metabolomics for class-wise identification of untargeted metabolomics data generated from high-resolution MS. Using this approach, we identified and validated the levels of several lipids in mouse serum that were significantly altered following Alum administration. These lipids showed a biphasic response even 168 h after vaccination. The majority of the lipids were triglycerides (TAGs), where TAGs with long-chain unsaturated fatty acids (FAs) decreased at 24 h and TAGs with short-chain FAs decreased at 168 h. To our knowledge, this is the first report on the impact of human vaccine adjuvant Alum on the host metabolome, which may provide new insights into the mechanism of action of Alum. ©
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| 39. |
- Johansson, Staffan, 1976, et al.
(författare)
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Mechanistic Proposal for the Formation of Specific Immunogenic Complexes via a Radical Pathway: A Key Step in Allergic Contact Dermatitis to Olefinic Hydroperoxides
- 2009
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Ingår i: Chem. Res. Toxicol.. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 22:11, s. 1774-1781
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Tidskriftsartikel (refereegranskat)abstract
- The widespread use of scented products causes an increase of allergic contact dermatitis to fragrance compounds in Western countries today. Many fragrance compounds are prone to autoxidation, forming hydroperoxides as their primary oxidation products. Hydroperoxides are known to be strong allergens and to form specific immunogenic complexes. However, the mechanisms for the formation of the immunogenic complexes are largely unknown. We have investigated this mechanism for (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH) by studying the formation of adducts in the reaction between this hydroperoxide and 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) in the presence of protected cysteine (NAc-Cys-OMe) or glutathione (GSH). Isolated adducts originate from the addition of the thiol group of NAc-Cys-OMe over the carbon−carbon double bonds of carvone. Furthermore, adducts between NAc-Cys-OMe and carveol as well as between GSH and carvone have been identified. The formation of these adducts most likely proceeds via the radical thiol−ene mechanism. The addition of a terpene moiety to cysteine offers an explanation of the specificity of the immune response to structurally different hydroperoxides. These results also explain the lack of cross-reactivity between carvone and Lim-2-OOH. In conclusion, we propose that immunogenic complexes of olefinic hydroperoxides can be formed via the radical thiol−ene mechanism. These complexes will be specific for the individual olefinic hydroperoxides due to the inclusion of a terpene moiety derived from the hydroperoxide.
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| 40. |
- Sävman, Karin, 1960, et al.
(författare)
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Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions
- 2021
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Ingår i: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 43:5, s. 296-311
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Tidskriftsartikel (refereegranskat)abstract
- Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation. Thus, we investigated the effect of galectin-3 on microglia in vitro under normal as well as infectious and sterile inflammatory conditions, and the effect of galectin-3 on neonatal brain injury following an infectious challenge in vivo. Conditions mimicking infectious or sterile inflammation were evaluated in primary microglia cell cultures from newborn mice, using LPS (10 ng/mL) and TNF-alpha (100 ng/mL). The response to galectin-3 was tested alone or together with LPS or TNF-alpha. Supernatants were collected 24 h after treatment and analyzed for 23 inflammatory mediators including pro- and anti-inflammatory cytokines and chemokines using multiplex protein analysis, as well as ELISA for MCP-1 and insulin-like growth factor (IGF)-1. Phosphorylation of proteins (AKT, ERK1/2, I kappa B-alpha, JNK, and p38) was determined in microglia cells. Neonatal brain injury was induced by a combination of LPS and HI (LPS + HI) in postnatal day 9 transgenic mice lacking functional galectin-3 and wild-type controls. LPS and TNF-alpha induced pro-inflammatory (9/11 vs. 9/10) and anti-inflammatory (6/6 vs. 2/6) cytokines, as well as chemokines (6/6 vs. 4/6) in a similar manner, except generally lower amplitude of the TNF-alpha-induced response. Galectin-3 alone had no effect on any of the proteins analyzed. Galectin-3 reduced the LPS- and TNF-alpha-induced microglia response for cytokines, chemokines, and phosphorylation of I kappa B-alpha. LPS decreased baseline IGF-1 levels, and the levels were restored by galectin-3. Brain injury or microglia response after LPS + HI was not affected by galectin-3 deficiency. Galectin-3 has no independent effect on microglia but modulates inflammatory activation in vitro. The effect was similar under infectious and sterile inflammatory conditions, suggesting that galectin-3 regulates inflammation not just by binding to LPS or toll-like receptor-4. Galectin-3 restores IGF-1 levels reduced by LPS-induced inflammation, suggesting a potential protective effect on infectious injury. However, galectin-3 deficiency did not affect microglia activation and was not beneficial in an injury model encompassing an infectious challenge.
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