Tamoxifen counteracts the allergic immune response and improves allergen‐induced dermatitis in mice

Babina, Magda; Kirn, F.; Hoser, Dana; Ernst, Dennis; Rohde, Wolfgang; Zuberbier, Torsten; Worm, Margitta

doi:10.1111/j.1365-2222.2010.03472.x

Cited by 25 publications

(23 citation statements)

References 42 publications

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“…Conversely, T cells are viewed as an essential element of AD pathology , as is also illustrated by their non‐redundant nature in mouse AD models . Consequently, reductions in T cells are associated with a beneficial course of the disease . Here, we found a potent reduction in T‐cell infiltrates in the skin down to approximately one‐third of their density in the control group.…”

Section: Discussionmentioning

confidence: 54%

“…A pronounced T‐cell infiltrate is a hallmark of AD in mouse and man , and T cells are an invariable element in AD pathology in mouse models of the disease . Accordingly, a reduction in the T‐cell infiltrate commonly parallels clinical improvement in the skin . Therefore, and in the light of the profound changes in lesional lymphocytes observed here, the clinical unresponsiveness of the dermatitis to PI seemed somewhat counterintuitive.…”

Section: Resultsmentioning

confidence: 60%

“…OVA‐specific and total immunoglobulins (IgE, IgG1, IgA, IgM and IgG2a) were measured by ELISA . The concentrations of OVA‐specific antibodies were estimated by comparison to a standard curve prepared from pooled sera of OVA‐sensitized mice.…”

Section: Methodsmentioning

confidence: 99%

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Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Mudnakudu-Nagaraju

Babina

Worm

2013

Experimental Dermatology

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Proteasome inhibition (PI) has been reported to interfere with antibody-driven autoimmune diseases. The impact of PI on the allergic immune response and on skin diseases like atopic dermatitis (AD) has not been thoroughly explored, however. Here, we examined whether the PI bortezomib interferes with the allergic immune response and the severity of AD by using an established mouse model of allergen-driven dermatitis, to which bortezomib was applied after the establishment of systemic sensitization to ovalbumin. The treatment indeed resulted in a remarkable decrease in total and allergen-specific plasma cells/antibody-secreting cells, as evidenced by flow cytometry and ELISpot, respectively. This was accompanied by rapid reductions in serum antibody titres, including a prominent reduction of the IgE isotype. CD4+ and CD8+ cells were greatly diminished in lesional skin on immunohistological staining. The impressive effects at the level of immune modulation did not result in any improvement in the eczema, however. Following up on this unexpected result, we found that the skin itself was susceptible to bortezomib, by which it was instructed to lower the expression of critical skin barrier genes, especially transglutaminase-1 and filaggrin. Together, bortezomib eliminates plasma cells and decreases immunoglobulin responses, including allergenic IgE. Although anti-inflammatory effects are detectable in the skin, counter-regulatory effects from PI on resident skin cells likely undermine improvement in the eczema. These results caution against the therapeutic use of bortezomib for inflammatory skin disorders, which are characterized by inherently impaired barrier function, especially AD.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 60%

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Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Mudnakudu-Nagaraju

Babina

Worm

2013

Experimental Dermatology

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“…Babina and colleagues reported that tamoxifen is capable of inducing a shift from a cellular (T H 1) to a humoral (T H 2) immunity (19,20). Tamoxifen also induces latent TGFb in breast cancer cell lines (21) and prevents maturation of antigen-presenting cells (22).…”

Section: Introductionmentioning

confidence: 99%

L-BLP25 Vaccine plus Letrozole Induces a TH1 Immune Response and Has Additive Antitumor Activity in MUC1-Expressing Mammary Tumors in Mice

Mehta

Wurz

Burich

et al. 2012

Clinical Cancer Research

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Purpose: In this study, we examine the immunomodulatory effects and antitumor activity of tamoxifen and letrozole when combined with the human epithelial mucin (hMUC1)-specific vaccine, L-BLP25, in the hMUC1-expressing mammary tumor (MMT) mouse model.Experimental Design: Dose-finding studies were conducted for both tamoxifen and letrozole. Letrozole and L-BLP25 combination studies used 69 MMT female mice assigned to five groups: untreated, cyclophosphamide þ placebo, cyclophosphamide þ L-BLP25, letrozole 0.8 mg/kg, and cyclophosphamide þ L-BLP25 þ letrozole. Tamoxifen and L-BLP25 combination studies used 48 MMT female mice assigned to five treatment groups: untreated, cyclophosphamide þ placebo, cyclophosphamide þ L-BLP25, tamoxifen 50 mg/kg, and cyclophosphamide þ L-BLP25 þ tamoxifen 50 mg/kg group. Mice were injected subcutaneously with L-BLP25 (10 mg) weekly for 8 weeks. Serum cytokines were serially measured using a Luminex assay, whereas splenocytes at termination were analyzed by ELISpot to determine T-helper (T H )1/T H 2 polarization of immune response.Results: Daily oral doses of 50 and 0.8 mg/kg of tamoxifen and letrozole, respectively, resulted in a significant survival advantage over controls (P < 0.05). A predominant T H 1-polarized immune response in vaccinated mice was seen with or without tamoxifen or letrozole treatments. In the L-BLP25 plus letrozole treatment group, statistically significant (P < 0.05) additive antitumor activity was observed, whereas tamoxifen plus L-BLP25 was not significantly different (P > 0.05). Conclusion:The results of this study show that hormonal therapy does not interfere with L-BLP25-induced predominant T H 1 response, and the combination of L-BLP25 with letrozole has additive antitumor activity in the MMT mouse model.

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“…Dermatomyositis is an autoimmune disease that occurs more often in women and causes inflammation of the skin and muscles. In a recent study, Babina et al (63) found that tamoxifen treatment interfered with all aspects of the allergic immune response, leading to a reduction of allergen-specific immunoglobulin levels (IgE, IgG1 and IgG2a) and a skewing effect in the T cell compartment with the inhibition of IL-4 in mice sensitized with ovalbumin-alum by the intra-peritoneal route. Along with the systemic effects, there was a reduction in local pathologies like diminished epidermal thickness and decreased CD4+ and CD8+ cell infiltrates.…”

Section: Anti-estrogenic Drugs: Connections With Autoimmune Disordersmentioning

confidence: 99%

Immunomodulatory effects of anti-estrogenic drugs

Ray¹,

M²

2012

Acta Pharmaceutica

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Immunomodulatory effects of anti-estrogenic drugsThere are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulators by altering the function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.

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Tamoxifen counteracts the allergic immune response and improves allergen‐induced dermatitis in mice

Abstract: TX inhibits allergic responses when given preventively and also therapeutically, and improves allergen-induced dermatitis. Because of its effectiveness, TX could bear significant therapeutic potential for the treatment of allergies.

Cited by 25 publications

References 42 publications

Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

L-BLP25 Vaccine plus Letrozole Induces a TH1 Immune Response and Has Additive Antitumor Activity in MUC1-Expressing Mammary Tumors in Mice

Immunomodulatory effects of anti-estrogenic drugs

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