| 1. |
- Rogers, Lisa M, et al.
(författare)
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Palmitate induces apoptotic cell death and inflammasome activation in human placental macrophages.
- 2020
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 90, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- There is an increasing prevalence of non-communicable diseases worldwide. Metabolic diseases such as obesity and gestational diabetes mellitus (GDM) increasingly affect women during pregnancy, which can harm pregnancy outcomes and the long-term health and wellbeing of exposed offspring. Both obesity and GDM have been associated with proinflammatory effects within the placenta, the critical organ governing fetal development.The purpose of these studies was to model, in vitro, the effects of metabolic stress (high levels of glucose, insulin and saturated lipids) on placental macrophage biology, since these cells are the primary innate immune phagocyte within the placenta with roles in governing maternofetal immune tolerance and antimicrobial host defense. Macrophages were isolated from the villous core of term, human placentae delivered through nonlaboring, elective Cesarean sections and exposed to combinations of elevated glucose (30mM), insulin (10nM) and the saturated lipid palmitic acid (palmitate, 0.4mM).We found that palmitate alone induced the activation of the nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in placental macrophages, which was associated with increased interleukin 1 beta release and an increase in apoptotic cell death. Glucose and insulin neither provoked these effects nor augmented the impact of palmitate itself.Our findings confirm an impact of saturated fat on placental macrophage immune activation and could be relevant to the impact of metabolic stress in vivo.
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| 2. |
- Kockum, I., et al.
(författare)
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Complex interaction between HLA DR and DQ in conferring risk for childhood type 1 diabetes
- 1999
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Ingår i: European Journal of Immunogenetics. - : Wiley. - 0960-7420 .- 1365-2370. ; 26:5, s. 361-372
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR and DQ factors, but the primary risk alleles are difficult to identify because recombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks were observed for DQB1*02-DQA1*0501/DQB1*0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and DQB1*0302 (AR 1/52, P < 0.001). Stratification analysis showed that DQB1*0302 was more frequent among DRB1*04 patients than DRB1*04 controls (P < 0.001), while DRB1*03 was more frequent among both DQA1*0501 (P < 0.001) and DQB1*02 (P < 0.001) patients than respective controls. The predispositional allele test indicated that DRB1*03 (P < 0.001) would be the predominant risk factor on the DRB1*03-DQA1*0501-DQB1*02 haplotype. In contrast, although DQB1*0302 (P < 0.001) would be the predominant risk factor on the DRB1*04-DQA1*0301-DQB1*0302 haplotype, the predispositional allele test also showed that DRB1*0401, but no other DRB1*04 subtype, had an additive risk to that of DQB1*0302 (P < 0.002). It is concluded that the association between type 1 diabetes and HLA is due to a complex interaction between DR and DQ since (1) DRB1*03 was more strongly associated with the disease than DQA1*0501-DQB1*02 and (2) DRB1*0401 had an additive effect to DQB1*0302. The data from this population-based investigation suggest an independent role of DR in the risk of developing type 1 diabetes, perhaps by providing diseases-promoting transcomplementation molecules.
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| 3. |
- Kockum, I., et al.
(författare)
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POPULATION ANALYSIS OF PROTECTION BY HLA‐DR AND DQ GENES FROM INSULIN‐DEPENDENT DIABETES MELLITUS IN SWEDISH CHILDREN WITH INSULIN‐DEPENDENT DIABETES AND CONTROLS
- 1995
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Ingår i: International Journal of Immunogenetics. - 1744-3121. ; 22:6, s. 443-465
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Tidskriftsartikel (refereegranskat)abstract
- A negative association between insulin‐dependent diabetes mellitus (IDDM) and HLA‐DR, DQA1 or DQB1 was found in a large population‐based investigation of childhood‐onset patients (more than 420 patients) and controls (more than 340 controls) from Sweden. The relative risk was decreased for several haplotypes that were negatively associated with IDDM: DR15‐DQA1*0102‐DQB1*0602, DR7‐DQA1*0201‐DQB1*0303, DR14‐DQA1*0101‐DQB1*0503, DRI1‐DQAI*0501‐DQB1*0301, DR13‐DQA1*0103‐DQB1*0603 and DR4‐DQA1*0301‐DQB1*0301. In a relative predispositional effect (RPE) analysis, however, only the DR15‐DQA1*0102‐DQB1*0602 haplotype was significantly decreased, which suggests that the major protective effect for IDDM is carried by this haplotype. This was supported by the observation that all genotypes which were negatively associated with IDDM, except DR7/13, included at least one allele from the DR15‐DQA1*0102‐DQB1*0602 haplotype. Relative predispositional effect (RPE) analysis of genotypes showed further that the DR15‐DQA1*0102‐DQB1*0602 haplotype was also negatively associated with IDDM when combined with any other haplotype, whether negatively or positively associated with IDDM. This supports previous suggestions that DR15‐DQA1*0102‐DQB1*0602 acts dominantly. However, both the stratification and the predispositional allele test failed to distinguish the negative association between IDDM and DR15 from that of DQBT0602. On the other hand, these tests indicated that DQA1*0102 was not likely to explain the negative association between IDDM and the DR15‐DQA1*0102‐DQB1*0602 haplotype. We conclude that the
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| 4. |
- Wassmuth, R., et al.
(författare)
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HLA DR AND DQ RFLP ANALYSIS IN CROHN'S DISEASE
- 1993
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Ingår i: International Journal of Immunogenetics. - 1744-3121. ; 20:5, s. 429-433
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Tidskriftsartikel (refereegranskat)abstract
- A study of 109 Swedish patients and 85 healthy Swedish controls with Crohn's disease (CD) by HLA class II RFLP genotyping was carried out. There was no significant association for any single DR or DQ specificity or phenotypic combination of DR and/or DO specificities among our study group of Caucasian extraction.
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