Effects of Raloxifene, a Selective Estrogen Receptor Modulator, on Thymus, T Cell Reactivity, and Inflammation in Mice

Erlandsson, Malin C.; Gömöri, Éva; Taube, Maria Beatriz Puzzi; Carlsten, Hans

doi:10.1006/cimm.2000.1719

Cited by 38 publications

(44 citation statements)

References 32 publications

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“…The inconsistency between our study and previous studies might be dependent on different doses used and different administration routes. However, when comparing OE 2 and raloxifene analogue effects, a significant difference between the two compounds is found in regards to thymic weight (Erlandsson et al 2000, Garcia-Perez et al 2006, with OE 2 being the most potent compound, supporting our data. Interestingly, when examining the capacity to activate the classical oestrogenic pathway, both OE 2 and raloxifene resulted in a significant increase in luciferase activation.…”

Section: Discussionsupporting

confidence: 88%

“…In addition, oestrogenic compounds, including raloxifene, have also been reported to result in variable degree of thymic atrophy (Buelke-Sam et al 1998, Erlandsson et al 2000, Yellayi et al 2002, Garcia-Perez et al 2006. In our study, OE 2 resulted in a dramatic decrease in thymus weight, while no thymic atrophy was detected after treatment with the raloxifene analogue LY117018.…”

Section: Discussionsupporting

confidence: 48%

“…In thymus, an organ important for the immune system, OE 2 treatment results in involution (Erlandsson et al 2000). In addition, oestrogenic compounds, including raloxifene, have also been reported to result in variable degree of thymic atrophy (Buelke-Sam et al 1998, Erlandsson et al 2000, Yellayi et al 2002, Garcia-Perez et al 2006.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, there is a discrepancy between treatment effects on thymus weight and activation of the classical signalling pathway. Raloxifene is known to affect T cell differentiation and various T cell subpopulation (Erlandsson et al 2000), effects that are not necessarily reflected by thymic weight. Thus, these raloxifene effects may be mediated via classical signalling.…”

Section: Discussionmentioning

confidence: 99%

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In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

Engdahl

Jochéms

Gustafsson

et al. 2009

Journal of Endocrinology

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Raloxifene is a selective oestrogen receptor modulator with tissue-specific effects. The mechanisms behind the effects of raloxifene are partly unclear, and the aim of the present study was to investigate whether raloxifene can activate the classical oestrogen-signalling pathway in vivo in three known oestrogen-responsive organs, uterus (reproductive organ), bone (non-reproductive organ) and thymus (immune organ). For this purpose, we have used reporter mice with a luciferase gene under control of oestrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription via the classical oestrogen pathway. Three-month-old ovariectomized ERE-luciferase mice were treated with the raloxifene analogue (LY117018), oestradiol (OE 2 ) or vehicle for 3 weeks. Luciferase activation was measured in bone, uterus and thymus, and compared to bone parameters, and uterus and thymus weights. The raloxifene analogue affected bone mineral density (BMD) to the same extent as OE 2 , and both treatments resulted in increased luciferase activity in bone. As expected, OE 2 treatment resulted in increased uterus weight and increased uterine luciferase activity, while the effect of LY117018 on uterus weight and luciferase activity was modest and significantly lower than the effect of OE 2 . LY117018 and OE 2 treatment resulted in similar luciferase activation in thymus. However, only OE 2 treatment resulted in thymic atrophy, while no effect on thymus weight was seen after LY117018 treatment. In summary, the raloxifene analogue LY117018 can activate the classical oestrogen pathway in bone, uterus and thymus in vivo, and this activation is associated with BMD and uterus weight, but not thymus weight.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

Engdahl

Jochéms

Gustafsson

et al. 2009

Journal of Endocrinology

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show abstract

“…Control mice received only the vehicle (Miglyol 812; 100 l/mouse/day). The dosages of raloxifene and estradiol used in the present study have previously been shown to be equally effective in preventing osteoporosis in mice (22)(23)(24). LY117018 differs from raloxifene at only 1 site on the molecule, with a piperidine ring on the basic side chain instead of a pyrrolidine ring.…”

Section: Methodsmentioning

confidence: 77%

Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis

Jochéms

Islander

Kallkopf

et al. 2007

Arthritis & Rheumatism

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Objective. In postmenopausal rheumatoid arthritis (RA), both estrogen deficiency and the inflammatory disease contribute to the development of generalized osteoporosis. Hormone replacement therapy (HRT) with estradiol preserves bone mineral density (BMD) and ameliorates arthritis, but long-term therapy is no longer an option due to significant side effects. We therefore used a mouse model of human RA to test the hypothesis that a selective estrogen receptor modulator (SERM), the raloxifene analog LY117018, could be beneficial in the treatment of both arthritis and osteoporosis.Methods. Female DBA/1 mice were ovariectomized and arthritis was induced with collagen immunization. Mice received an injection of raloxifene, estradiol, or vehicle control, administered prophylactically or therapeutically, and thereafter the clinical arthritis score was evaluated continuously. At termination, BMD was analyzed with peripheral quantitative computed tomography. Paws were collected for histology, and sera were analyzed for cytokines and markers of bone and cartilage turnover. Levels of cytokine messenger RNA (mRNA) were investigated with real-time polymerase chain reaction.Results. Treatment with raloxifene dramatically decreased the frequency and severity of arthritis. Effective preservation of bone and cartilage was seen in raloxifene-exposed mice, as demonstrated by increased BMD and decreased serum levels of cartilage oligomeric matrix protein in the raloxifene-treated mice compared with controls. Decreased levels of mRNA for both tumor necrosis factor ␣ and RANKL in spleen cells from raloxifene-treated arthritic mice indicated an immunosuppressive action of this SERM.Conclusion. In a well-established model of postmenopausal RA, the raloxifene analog LY117018 potently inhibits the progression of arthritis and the associated development of osteoporosis, both in a prophylactic and in a therapeutic regimen. Since long-term HRT has been associated with significant side effects, raloxifene may be a useful adjuvant treatment for postmenopausal RA.

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Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints

Ocal

Kürüm

Karahan

et al. 2014

Journal of Pharmaceutical Sciences

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Effects of Raloxifene, a Selective Estrogen Receptor Modulator, on Thymus, T Cell Reactivity, and Inflammation in Mice

Cited by 38 publications

References 32 publications

In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

In vivo activation of gene transcription via oestrogen response elements by a raloxifene analogue

Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis

Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints

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