Bromocriptine restores tolerance in estrogen-treated mice

Peeva, Elena; Grimaldi, Christine; Spatz, Linda; Diamond, Betty

doi:10.1172/jci10420

Cited by 84 publications

(58 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, tamoxifen was able to abrogate the estradiol-induced rise in anti-dsDNA Ab titers and it alone did not act as an estrogen-receptor agonist in this model. Glomerular IgG deposition was detected only in the kidneys of estradiol-treated mice, confirming previous findings that estradiol treatment can induce production of nephritogenic autoantibodies (10,23) (Fig. 1b).…”

Section: Tamoxifen Abrogates An Estrogen-induced Lupus-like Phenotypesupporting

confidence: 90%

See 1 more Smart Citation

Tamoxifen Blocks Estrogen-Induced B Cell Maturation but Not Survival

Peeva

Jeganathan

Diamond

2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Estrogen treatment has been shown not only to exacerbate disease activity and accelerate death in spontaneous murine models of lupus but also to induce a lupus-like phenotype in nonspontaneously autoimmune mice. In mice transgenic for the H chain of an anti-DNA Ab, estrogen rescues naive autoreactive B cells that normally are deleted and causes them to mature to a marginal zone phenotype. Estrogen further leads to the activation of this population causing an elevation of serum anti-DNA Ab titers and renal disease. This study was designed to evaluate the therapeutic potential of tamoxifen, a selective estrogen receptor modulator, on estrogen-induced lupus. Mice treated with both estradiol and tamoxifen showed no elevation in anti-DNA Ab titers and consequently no glomerular IgG. The DNA-reactive B cell population that is rescued by estrogen was present in an anergic state in mice treated with both estradiol and tamoxifen. Estradiol enhances transitional B cell resistance to apoptosis and expands the population of marginal zone B cells; tamoxifen did not impede the enhanced resistance to apoptosis, but prevented the development of autoreactive cells as marginal zone B cells. Thus, estrogen-induced autoimmunity proceeds through two distinct molecular pathways, one affecting survival and the other maturation. Activation, but not survival, of autoreactive B cells can be abrogated by tamoxifen. Drugs that modulate even some of the effects of estrogen may be beneficial in patients with lupus. Eventually, understanding the pathways involved in survival and activation of autoreactive B cells will permit the development of therapeutics that target all relevant pathways.

show abstract

Section: Tamoxifen Abrogates An Estrogen-induced Lupus-like Phenotypesupporting

confidence: 90%

“…ELISAs for anti-DNA reactivity in serum and culture supernatant were performed as previously described using calf thymus dsDNA (23).…”

Section: Elisasmentioning

confidence: 99%

Tamoxifen Blocks Estrogen-Induced B Cell Maturation but Not Survival

Peeva

Jeganathan

Diamond

2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…BRC treatment reduced disease symptoms and delayed lupus-related death, which results primarily from glomerulonephritis (immunoglobulin deposits) in the kidney (McMurray, 2001). Recent animal studies suggest that E2-treated transgenic animals develop a lupus-like phenotype with an expansion in autoreactive B cells (a breakdown of tolerance) and elevation in antibody production (Peeva et al, 2000;Grimaldi et al, 2001). This E2 effect requires the presence of PRL as BRC treatment reduced antibody production (Peeva et al, 2000).…”

Section: B Prolactin and Autoimmune Diseasesmentioning

confidence: 99%

Prolactin Modulation of Immune and Inflammatory Responses

Yu-Lee¹

2002

Recent Progress in Hormone Research

186

View full text Add to dashboard Cite

Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL, PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)B signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.

show abstract

“…The apparent decreased, rather than increased, presence of prolactin in chlordecone-treated mice has interesting implications in terms of the comparative mechanisms by which these two agents affect autoimmunity. For example, it has been shown that without the help of prolactin, E2 can still mediate the survival of autoreactive B cells, but loses its ability to activate these anergic B cells [22]. We reported earlier that both chlordecone and E2 share the same features in reducing apoptosis of B cells in germinal center, a place where negative selection of autoreactive B cells occurs [24].…”

Section: Discussionmentioning

confidence: 94%

“…Recent studies showed that the immunostimulatory effects of E2 are directly associated with the presence of prolactin. Treatment with the dopamine agonist bromocriptine, which blocks prolactin secretion, prevented exogenous E2 from breaking tolerance and accelerating autoimmunity in murine models [21,22]. Further, high prolactin and low E2 states have been reported to increase autoimmunity, while high E2 and low prolactin states did not [21], providing additional support for the postulate that prolactin plays a critical role in E2 effects in accelerating autoimmunity in mice.…”

Section: Introductionmentioning

confidence: 81%

Diminished prolactin from chlordecone treatment in ovariectomized (NZB×NZW)F1 mice

Wang¹,

Roberts²,

Butfiloski³

et al. 2007

International Immunopharmacology

View full text Add to dashboard Cite

In murine models of systemic lupus erythematosus (SLE), administration of either prolactin or estradiol (E2) increases autoimmunity, and there is evidence that elevated prolactin in response to E2 administration may contribute substantially to E2 effects. Hormonal influence on SLE can extend to environmental agents, as demonstrated by the ability of estrogenic organochlorine pesticides such as chlordecone to accelerate the development of lupus in female (NZB x NZW)F 1 mice. In order to evaluate a potential role for prolactin in chlordecone effects on SLE, it was necessary to first determine whether treatment with chlordecone, like E2, results in elevated prolactin levels. Ovariectomized (NZB x NZW)F 1 mice were treated for 5-6 weeks with chlordecone or E2 in doses shown previously to significantly shorten the time to onset of SLE. At the end of the treatment period, serum prolactin levels were increased 10-to 20-fold in E2-treated mice compared to untreated controls, but decreased in an apparent dose-dependent manner in mice treated with chlordecone. Prolactin receptor in purified B and CD4 T cells from treated animals, assessed through measurement of mRNA using quantitative real-time PCR, was increased by E2 treatment but unchanged in response to chlordecone. These observations suggest that the role of prolactin in eliciting autoimmunity in E2-treated animals is absent in the case of chlordecone, and by implication, that chlordecone possesses other actions that can replace the contribution of prolactin to development of SLE.

show abstract

Bromocriptine restores tolerance in estrogen-treated mice

Cited by 84 publications

References 46 publications

Tamoxifen Blocks Estrogen-Induced B Cell Maturation but Not Survival

Tamoxifen Blocks Estrogen-Induced B Cell Maturation but Not Survival

Prolactin Modulation of Immune and Inflammatory Responses

Diminished prolactin from chlordecone treatment in ovariectomized (NZB×NZW)F1 mice

Contact Info

Product

Resources

About