| 1. |
- López-Ferreras, Lorena, et al.
(author)
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Ghrelin's control of food reward and body weight in the lateral hypothalamic area is sexually dimorphic
- 2017
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In: Physiology & Behavior. - : Elsevier BV. - 0031-9384. ; 176, s. 40-49
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Journal article (peer-reviewed)abstract
- Ghrelin is a stomach-produced hormone that stimulates ingestive behavior and increases motivated behavior to obtain palatable foods. Ghrelin receptors (growth hormone secretagogue receptors; Ghsr) are expressed in the lateral hypothalamic area (LHA), and LHA-targeted ghrelin application increases ingestive behavior in male rodents. However, the effects of LHA ghrelin signaling in females are unexplored. Here we investigated whether LHA ghrelin signaling is necessary and sufficient for control of ingestive and motivated behavior for food in male and female rats. Ghrelin delivered to the LHA increased food intake and motivated behavior for sucrose in both male and female rats, whereas increased food-seeking behavior and body weight were only observed in females. Females had slightly higher Ghsr levels in the LHA compared to males, and importantly, acute blockade of the Ghsr in the LHA significantly reduced food intake, body weight, and motivated behavior for sucrose in female but not male rats. Chronic LHA Ghsr reduction in female rats achieved by RNA inference-mediated Ghsr knockdown, resulting in a 25% reduction in LHA Ghsr mRNA, abolished the reward-driven behavioral effects of LHA-targeted ghrelin, but was not sufficient to affect baseline food intake or food reward responding. Collectively we show that ghrelin acts in the LHA to alter ingestive and motivated behaviors in a sex-specific manner. (C) 2017 The Authors. Published by Elsevier Inc.
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| 2. |
- Ulleryd, Marcus A, et al.
(author)
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RNA sequencing data describing transcriptional changes in aorta of ApoE-/mice after alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) stimulation
- 2020
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In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 30
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Journal article (peer-reviewed)abstract
- This manuscript is a companion paper to Ulleryd M.U. et al., "Stimulation of alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) inhibits atherosclerosis via immunomodulatory effects on myeloid cells" Atherosclerosis, 2019 [1]. Data shown here include RNA sequencing data from whole aorta of ApoE-/- mice fed high fat diet and treated with the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) agonist AZ6983 for 8 weeks using subcutaneously implanted osmotic minipumps. Here we present the top gene networks affected by treatment with AZ6983, as well as the up- and down-regulated genes in aorta after treatment. Further, a URL link to the RNA sequencing datasets submitted to GEO is included. (C) 2020 The Authors. Published by Elsevier Inc.
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| 3. |
- Magnusson, Sofia, 1980-, et al.
(author)
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Amelioration of collagen-induced arthritis by human recombinant soluble FcγRIIb
- 2008
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In: Clinical Immunology. - : Elsevier BV. - 1521-6616 .- 1521-7035. ; 127:2, s. 225-233
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Journal article (peer-reviewed)abstract
- Immune complex (IC) binding to Fc gamma receptors (FcγRs) is central for inflammatory reactions seen in autoimmune diseases. Consequently, a therapeutic agent with a possibility to interfere with binding of pathogenic IC to FcγRs would be valuable in autoimmune disorders such as rheumatoid arthritis (RA). Here we have explored the therapeutic effect of a recombinant solublehuman FcγRIIb (sFcγRIIb) protein in collagen-induced arthritis (CIA). In vitro studies of the sFcγRIIb demonstrated binding to mouse IgG, suggesting that sFcγRIIb can absorb pathogenic IgG anticollagen type II (CII) IC in vivo. Hence, administration of sFcγRIIb significantly reduced CIA severity compared to control treated mice. The sFcγRIIb treated mice had significantly less IgG anti-CII antibodies in serum and lowermRNA levels of inflammatory cytokines compared to controlmice. In conclusion, sFcγRIIb treatment ameliorates CIA by reducing IC-stimulated inflammation and joint swelling. This suggests that recombinant sFcγRIIb may be useful as therapeutic agent in RA.
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| 4. |
- Nilsson, Kajsa E., et al.
(author)
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Enhanced susceptibility to low-dose collagen-induced arthritis in CR1/2-deficient female mice : possible role of estrogen on CR1 expression
- 2009
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 23:8, s. 2450-2458
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Journal article (peer-reviewed)abstract
- The influence of complement receptor 1 and 2 (CR1/2) was investigated on the susceptibility to low-dose collagen-induced arthritis (CIA) in wild-type (WT) and CR1/2-deficient DBA/1 mice. Significantly enhanced CIA was observed in female CR1/2-deficient mice compared with WT female mice, while male mutant and WT mice showed similar arthritis development. The enhanced CIA was accompanied with higher complement levels and a prolonged IgM anti-collagen type II response. When investigating whether estrogen contributed to the different arthritis susceptibility, we found that ovariectomy rendered WT females more sensitive to low-dose CIA and to the same extent as CR1/2-deficient females, while CR1/2-deficient mice were unaffected by ovariectomy. Notably, the ovariectomized WT mice displayed reduced CR1(+) B220(+) B-cell numbers and CR1 expression compared with sham-operated WT mice, suggesting a stimulatory effect of estrogen on CR1. In accordance, a significant correlation was observed between reduced CR1 expression in B cells and increased age in healthy female blood donors but not in male donors. Our findings demonstrate an important role of CR1/2 in suppressing CIA in female mice under low-antigen conditions. The data suggest that estrogen promote CR1 expression in B cells. These findings provide insight to the increased frequency of rheumatoid arthritis in postmenopausal women.
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| 5. |
- Svensson, Per-Arne, 1969, et al.
(author)
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Gene expression in human brown adipose tissue.
- 2011
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In: International journal of molecular medicine. - : Spandidos Publications. - 1791-244X .- 1107-3756. ; 27:2, s. 227-32
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Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) has profound effects on body weight and metabolism in rodents. Recent reports show that human adults have significant amounts of BAT. Our aim was to study the gene expression profile of human BAT. Biopsies of adipose tissue with brown-red color and subcutaneous white adipose tissue (WAT) were obtained from 24 patients undergoing surgery in the thyroid region. Intrascapular BAT and epididymal WAT biopsies were obtained from 10 mice. Expression was analyzed by DNA microarray, real-time PCR and immunohistochemistry. Using the expression of the brown adipocyte-specific gene uncoupling protein 1 (UCP1) as a marker, approximately half of the human brown-red adipose tissue biopsies taken in the thyroid region contained BAT, and the presence of cells with brown adipocyte morphology was also verified by histology. Microarray analysis of 9 paired human BAT and WAT samples showed that 17 genes had at least a 4-fold higher expression in BAT compared to WAT and five of them (CKMT1, KCNK3, COBL, HMGCS2, TGM2) were verified using real-time PCR (P<0.05 for all). In addition, immunohistochemistry showed that the UCP1, KCNK3 and CKMT1 proteins are expressed in brown adipocytes. Except for UCP1 and KCNK3, the genes overexpressed in human BAT were not overexpressed in mouse BAT compared to mouse WAT. Our analysis identified genes that are differentially expressed in human BAT compared to WAT. The results also show that there are species-specific differences in BAT gene expression and this emphasizes the need for further molecular characterization of human BAT to clarify the mechanisms involved in regulated heat production in humans.
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| 6. |
- Ulleryd, Marcus A, et al.
(author)
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Stimulation of alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibits atherosclerosis via immunomodulatory effects on myeloid cells.
- 2019
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In: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 287, s. 122-133
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Journal article (peer-reviewed)abstract
- Alpha 7 nicotinic acetylcholine receptor (α7nAChR) stimulation can regulate acute inflammation, and lack of α7nAChR accelerates atherosclerosis in mice. In this study, we aimed to investigate the effects of the novel α7nAChR agonist, AZ6983, on atherosclerosis and assess its possible immunomodulating effects.AZ6983 was tested in vitro in LPS-challenged mouse and human blood and in vivo using the acute inflammatory air pouch model. Thereafter, long-term effects of AZ6983 treatment on atherosclerosis and immune responses were assessed in apoE-/- mice after 8 and 12 weeks. Atherosclerosis was investigated in the aortic root and thoracic aorta, serum levels of cytokines were analysed and RNAseq was used to study aortic gene expression. Further, bone-marrow-derived macrophages were used to assess phagocytosis in vitro.α7nAChR activation by AZ6983 decreased pro-inflammatory cytokines in acute stimulations of human and mouse blood in vitro, as well as in vivo using the air pouch model. Treating apoE-/- mice with AZ6983 decreased atherosclerosis by 37-49% and decreased serum cytokine levels. RNAseq analysis of aortae suggested the involvement of several specific myeloid cell functions, including phagocytosis. In line with this, AZ6983 significantly increased phagocytosis in bone marrow-derived macrophages.This study demonstrates that activation of α7nAChR with AZ6983 inhibits atherosclerosis in apoE-/-mice and that immunomodulating effects on myeloid cells, such as enhanced phagocytosis and suppression of inflammatory cytokines, could be part of the athero-protective mechanisms. The observed anti-inflammatory effect in human blood supports the idea that AZ6983 may decrease disease also in humans.
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| 7. |
- Wernersson, Sara, et al.
(author)
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Age-related enlargement of lymphoid tissue and altered leukocyte composition in serglycin-deficient mice
- 2009
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In: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 85:3, s. 401-408
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Journal article (peer-reviewed)abstract
- Serglycin (SG) is a proteoglycan that is located predominantly in the secretory granules of hematopoietic cells. Previous studies have established a crucial role for SG in promoting the storage of various secretory granule compounds that are of importance in the immune defense system. Here, we show that mice lacking SG spontaneously develop enlargement of multiple lymphoid organs, including the spleen, Peyer's patches (PP), and bronchus-associated lymphoid tissue. In the spleen, the lack of SG resulted in a significant decrease in the proportion of CD4(+) cells as well as an increase of the CD45RC(+) leukocyte population, indicating an expansion of naïve lymphocytes. In the PP, the lack of SG resulted in a general increase in cellularity, without significant alterations in the proportion of individual leukocyte populations. The enlargement of lymphoid tissues was not accompanied by increased serum levels of inflammatory cytokines. The number of mast cells in the peritoneum was not affected by the lack of SG, as judged by surface staining for CD117 (c-kit). However, the intensity of c-kit staining was reduced significantly in SG null animals. Moreover, the number of peritoneal macrophages, defined by morphological criteria and by CD11b staining, was decreased markedly in older, SG-deficient animals. Finally, experiments in which airway inflammation was induced by bacterial LPS revealed a more pronounced inflammatory response in old, SG-deficient as compared with wild-type mice. Taken together, our data show that SG deficiency causes multiple, age-related effects on the lymphoid system.
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