Environmental and Endogenous Peroxisome Proliferator-Activated Receptor γ Agonists Induce Bone Marrow B Cell Growth Arrest and Apoptosis: Interactions between Mono(2-ethylhexyl)phthalate, 9-<i>cis</i>-Retinoic Acid, and 15-Deoxy-Δ12,14-prostaglandin J2

Schlezinger, Jennifer J.; Howard, Gregory J.; Hurst, Christopher H.; Emberley, Jessica K.; Waxman, David J.; Webster, Thomas F.; Sherr, David H.

doi:10.4049/jimmunol.173.5.3165

Cited by 40 publications

(32 citation statements)

References 80 publications

(105 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, we observed that T. cruzi infection triggers prostaglandin secretion by CD11b + myeloid cells within the BM compartment. On the other hand, by exogenously adding prostaglandin to different B cell lines, it was demonstrated that prostaglandins selectively induce apoptosis of immature B cells [24,45]. Herein, we highlight the biological importance of this phenomenon by demonstrating for the first time the impact of Cox products on immature B cells during a protozoan infection.…”

Section: Discussionmentioning

confidence: 87%

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

et al. 2005

View full text Add to dashboard Cite

The ability of a microorganism to elicit or evade B cell responses represents a determinant factor for the final outcome of an infection. Although pathogens may subvert humoral responses at different stages of B cell development, most studies addressing the impact of an infection on the B cell compartment have focused on mature B cells within peripheral lymphoid organs. Herein, we report that a protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of immature B cells in the BM, which also compromises recently emigrated B cells in the periphery. The depletion of BM immature B cells is associated with an increased rate of apoptosis mediated by a parasite-indirect mechanism in a Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an important role in B cell depletion, since CD11b + BM cells from infected mice secrete a product of the cyclooxygenase pathway that eliminates immature B cells. These results highlight a previously unrecognized maneuver used by a protozoan parasite to disable B cell generation, limiting host defense and favoring its chronic establishment.

show abstract

Section: Discussionmentioning

confidence: 87%

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Limited information has been reported on the effect of phthalates on the immune system, where phthalate ester metabolites have been reported to be peroxisome proliferator-activated receptor γ (PPARγ) agonists capable of inducing apoptosis on primary bone marrow B cells (Schlezinger et al 2004). Cells from the immune system such as lymphoblasts are crucial to the adaptive cellular immune response based in a dynamic antigen pathogen recognition system.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial permeability and toxicity of diethylhexyl and monoethylhexyl phthalates on TK6 human lymphoblasts cells

Rosado-Berrios

Vélez

Zayas

2011

Toxicology in Vitro

View full text Add to dashboard Cite

Phthalates are ubiquitous compounds used in the manufacturing industry. Some are known endocrine disruptors, acting as xenoestrogens, others induce reproductive toxicity and damage to DNA among other effects. Studies on apoptosis induction and mitochondrial damage capacity of phthalates on the immune system are limited. This study aims to determine cell viability inhibition and apoptosis induction of diethylhexyl phthalate (DEHP) and monoethylhexyl phthalate (MEHP) on the human TK6 lymphoblast cell line at concentrations found in the environment. Key hallmark events, such as mitochondrial membrane permeability, generation of reactive oxygen species (ROS) and activation of caspase 3 and 7 were measured. Concentrations that inhibit viability of 50% (IC50) of the cells were determined at 24, 48 and 72 hours with doses ranging from 10μM to 500μM. Changes in mitochondrial membrane permeability, ROS generation and activation of caspases 3 and 7, were measured as part of the cell death mechanism. The IC50 at 24 hours was approximately 250 μM for both phthalates; at 48 hours were 234μM and 196μM for DEHP and MEHP, respectively and at 72 hours IC50s were 100 μM and 80 μM for DEHP and MEHP respectively. Overall the longer the time of exposure the lower the IC50's for both compounds. Both compounds affected mitochondrial membrane potential, promoted ROS generation and activated caspases 3 and 7. MEHP is more toxic, promotes higher level of ROS production and caspases activation. Our findings suggest that DEHP and MEHP have the capacity to induce apoptosis in cells of the immune system at concentrations found in the environment.

show abstract

“…We previously reported that human eosinophils expressed peroxisome proliferator-activated receptor ␥ (PPAR␥), a heterodimer partner of RXR, and that stimulation of eosinophils with a synthetic PPAR␥ agonist inhibited IL-5-induced eosinophil survival by leading apoptosis (22). Based on previous reports that the PPAR␥ agonist-induced apoptotic effect was increased by cotreatment with the agonist for RXR (36) or with 9-cis-RA (37), we initially speculated that PPAR␥/RXR activation by each agonist synergistically induced eosinophil apoptosis. However, contrary to our expectation, a preliminary study revealed that cotreatment of eosinophils with 9-cis-RA and a synthetic PPAR␥ agonist prolonged cell survival.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acids Are Potent Inhibitors of Spontaneous Human Eosinophil Apoptosis

Ueki

Mahemuti

Oyamada

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Retinoic acids (RAs), which are active metabolites of vitamin A, are known to enhance Th2-type immune responses in vitro, but the role of RAs in allergic inflammatory cells remains unclear. In this study, we demonstrated that purified peripheral blood eosinophils expressed nuclear receptors for RAs at the mRNA and protein levels. Eosinophils cultured with all-trans RA (ATRA) and 9-cis-RA showed dramatically induced cell survival and nuclear hypersegmentation, and the efficacy of RAs (10−6M) was similar to that of IL-5 (1 ng/ml), the most critical cytokine for eosinophil activation. Pharmacological manipulation with receptor-specific agonists and antagonists indicated that the antiapoptotic effect of RAs was mediated through ligand-dependent activation of both retinoid acid receptors and retinoid X receptors (mainly retinoid acid receptors). Furthermore, using a gene microarray and a cytokine Ab array, we discovered that RAs induced vascular endothelial growth factor, M-CSF, and MCP-1 secretion, although they were not involved in eosinophil survival. RA-induced eosinophil survival appears to be associated with down-regulation of caspase 3 and inhibition of its enzymatic activity. These findings indicate an important role of RAs in homeostasis of granulocytes and provide further insight into the cellular and molecular pathogenesis of allergic reactions.

show abstract

Environmental and Endogenous Peroxisome Proliferator-Activated Receptor γ Agonists Induce Bone Marrow B Cell Growth Arrest and Apoptosis: Interactions between Mono(2-ethylhexyl)phthalate, 9-cis-Retinoic Acid, and 15-Deoxy-Δ12,14-prostaglandin J2

Cited by 40 publications

References 80 publications

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

Mitochondrial permeability and toxicity of diethylhexyl and monoethylhexyl phthalates on TK6 human lymphoblasts cells

Retinoic Acids Are Potent Inhibitors of Spontaneous Human Eosinophil Apoptosis

Contact Info

Product

Resources

About