High Physiological Concentrations of Progesterone Reverse Estradiol-Mediated Changes in Differentiation and Functions of Bone Marrow Derived Dendritic Cells
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{"title"=>"High physiological concentrations of progesterone reverse estradiol-mediated changes in differentiation and functions of bone marrow derived dendritic cells", "type"=>"journal", "authors"=>[{"first_name"=>"Fangming", "last_name"=>"Xiu", "scopus_author_id"=>"55321356900"}, {"first_name"=>"Varun C.", "last_name"=>"Anipindi", "scopus_author_id"=>"36917872600"}, {"first_name"=>"Philip V.", "last_name"=>"Nguyen", "scopus_author_id"=>"56346954600"}, {"first_name"=>"Jeanette", "last_name"=>"Boudreau", "scopus_author_id"=>"23479526000"}, {"first_name"=>"Hong", "last_name"=>"Liang", "scopus_author_id"=>"57199818164"}, {"first_name"=>"Yonghong", "last_name"=>"Wan", "scopus_author_id"=>"7402414436"}, {"first_name"=>"Denis P.", "last_name"=>"Snider", "scopus_author_id"=>"7102806516"}, {"first_name"=>"Charu", "last_name"=>"Kaushic", "scopus_author_id"=>"6701596430"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"609727175", "sgr"=>"84963765683", "issn"=>"19326203", "pmid"=>"27064901", "scopus"=>"2-s2.0-84963765683", "doi"=>"10.1371/journal.pone.0153304"}, "id"=>"b910cd09-bdc5-3e16-88ee-e94e3ca32f1a", "abstract"=>"Female sex steroids, estradiol (E2) and progesterone (P4), play a key role in regulating immune responses in women, including dendritic cell (DC) development, and functions. Although the two hormones co-occur in the body of women throughout the reproductive years, no studies have explored their complex combinatorial effects on DCs, given their ability to regulate each other's actions. We examined murine bone marrow derived dendritic cells (BMDC) differentiation and functions, in the presence of a wide range of physiological concentrations of each hormone, as well as the combination of the two hormones. E2 (10-12 to 10-8M) enhanced the differentiation of CD11b+CD11c+ DCs from BM precursor cells, and promoted the expression of CD40 and MHC Class-II, in a dose-dependent manner. In contrast, P4 (10-9 to 10-5M) inhibited DC differentiation, but only at the highest concentrations. These effects on BMDCs were observed both in the presence or absence of LPS. When both hormones were combined, higher concentrations of P4, at levels seen in pregnancy (10-6M) reversed the E2 effects, regardless of the concentration of E2, especially in the absence of LPS. Functionally, antigen uptake was decreased and pro-inflammatory cytokines, IL-12, IL-1 and IL-6 production by CD11b+CD11c+ DCs, was increased in the presence of E2 and these effects were reversed by high concentrations of P4. Our results demonstrate the distinct effects of E2 and P4 on differentiation and functions of bone marrow myeloid DCs. The dominating effect of higher physiological concentrations of P4 provides insight into how DC functions could be modulated during pregnancy.", "link"=>"http://www.mendeley.com/research/high-physiological-concentrations-progesterone-reverse-estradiolmediated-changes-differentiation-fun", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>1, "Student > Bachelor"=>3, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4935670"], "description"=>"<p>BM cells isolated from OVX mice were cultured with GM-CSF in the presence of E2 at a low (10<sup>-11</sup>M) (A) or high (10<sup>-9</sup>M) (B) concentration with varying doses of P4 (10<sup>-9</sup>M to 10<sup>-5</sup>M), with (dashed) or without (solid) LPS. At the end of culture, cells were harvested and stained with Abs to detect CD11b, CD11c, CD40 and MHCII. Data are percentages of CD11b<sup>+</sup>CD11c<sup>+</sup> DCs (top panels); percentages of CD40<sup>+</sup>/CD11b<sup>+</sup>CD11c<sup>+</sup>DCs (middle panels); and percentages of MHCII<sup>+</sup>/CD11b<sup>+</sup>CD11c<sup>+</sup> DCs (bottom panels). Data shown are Mean ± SD of 6 independent experiments. Statistical significance is indicated by *p<0.05; **p<0.01;*** p<0.001 compared with E2 only treated controls.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170368, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/High_doses_of_P4_reversed_effects_of_E2_in_presence_or_absence_of_LPS_treatment_/3170368", "title"=>"High doses of P4 reversed effects of E2 in presence or absence of LPS treatment.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935541"], "description"=>"<p>BM cell isolated from OVX mice were cultured in sex hormone-deficient medium with murine GM-CSF alone, or in the presence of varying concentrations of E2 (A, B, C, D). Initial gating for mononuclear cells is shown in (A). Data in (B, C, D) are from cells collected at end of culture, and stained with Abs for CD11b and CD11c. Representative dot plot data are shown in (B). Data for percentages of CD11b<sup>+</sup>CD11c<sup>+</sup> DCs from cultures with different concentrations of E2 and treated with (dashed) or without (solid) LPS are shown in (C). Absolute numbers of CD11b<sup>+</sup> CD11c<sup>+</sup> DCs cultured with different concentrations of E2 are shown in (D). Data shown is Mean ± SD of 6 independent experiments. Statistical significance is indicated by * p<0.05; **p<0.01; *** p<0.001 compared with untreated control.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170248, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_E2_on_the_differentiation_of_DC_from_BM_/3170248", "title"=>"Effects of E2 on the differentiation of DC from BM.", "pos_in_sequence"=>1, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935586"], "description"=>"<p>BM cell isolated from OVX mice were cultured in sex hormone-deficient medium with murine GM-CSF alone, or in the presence of varying concentrations of P4. Data in (A, B, C) are from cells collected at end of culture, and stained with Abs for CD11b and CD11c. Initial gating for monocytes as shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153304#pone.0153304.g001\" target=\"_blank\">Fig 1A</a>. Representative dot plot data are shown in (A). Percentages of CD11b<sup>+</sup>CD11c<sup>+</sup> APCs from cultures grown in presence of different concentrations of P4, treated with (dashed) or without (solid) LPS are shown in (B). Absolute numbers of CD11b<sup>+</sup> CD11c<sup>+</sup> APCs cultured with P4 are shown in (C). Data show Mean ± SD of 6 independent experiments. Statistical significance is indicated by * p<0.05; **p<0.01; *** p<0.001 compared with untreated control.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170281, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_P4_on_the_differentiation_of_APCs_from_BM_/3170281", "title"=>"Effects of P4 on the differentiation of APCs from BM.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935784"], "description"=>"<p>BM cells isolated from OVX mice were cultured with GM-CSF in the presence of varying doses of E2 or P4 or combination of both. On day 6, 5ng/ml LPS was added to the culture for 24hrs. Culture treated with LPS alone (+LPS-E2) was negative control and untreated culture (-LPS -E2) was background. The protein transport inhibitor (BD Golgi Plug) was added for the last 6 hrs of culture. Cells were stained for intracellular IL-12, TNF- α and IL-6 with respective APC-conjugated antibodies. The top panel in A is gating scheme and isotype control. The rest of the panels in A are the percentage of IL-12-secreting CD11b<sup>+</sup>CD11c<sup>+</sup> DCs by intracellular staining under experimental conditions. Percentage of CD11b+CD11c+ DCs positive for IL-12, TNF-α and IL-6 are showed in B, C and D, respectively. Data represent samples in triplicate from 2 independent determinations. *p<0.05; ** p<0.01; ***p<0.001 compared with non-hormone treated control or the comparison of combination treatment with single hormone treatment.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170476, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/High_dose_of_P4_inhibited_the_cytokine_secretion_from_E2_treated_BMDCs_/3170476", "title"=>"High dose of P4 inhibited the cytokine secretion from E2-treated BMDCs.", "pos_in_sequence"=>8, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935754"], "description"=>"<p>BM cells isolated from OVX mice were cultured with GM-CSF in the presence of varying doses of E2 or P4. On day 6, 5ng/ml LPS was added to the culture for further 24h culture and supernatants were collected and cytokine concentrations were determined (IL-12, IL-10, IL-8, IL-10, TNF-α, IFN-γ and IL-1β) by multi-analyte cytokine and chemokine assays. TGF-β in the supernatants was determined by ELISA. The values (pg/ml, mean ±SD) were normalized to the percentage of CD11b<sup>+</sup> CD11c<sup>+</sup> DCs in each treatment. Data represent triplicate samples from 2 independent experiments. Statistical significance is indicated by *p<0.05; ** p<0.01; ***p<0.001 compared with untreated control.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170449, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/E2_and_P4_induced_different_cytokine_secretion_profile_from_BMDCs_/3170449", "title"=>"E2 and P4 induced different cytokine secretion profile from BMDCs.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935631"], "description"=>"<p>BM cell isolated from OVX mice were cultured in sex hormone-deficient medium with murine GM-CSF alone, or in the presence of varying concentrations of E2 (A, B) or P4 (C, D). At end of culture, cells were collected and stained with Abs for CD11b, CD11c, MHC II and CD40 antibodies. Cell culture were treated with (dashed) or without (solid) LPS for last 24 hrs. Y axis represents the percentage of CD40+ (A, C) or MHCII+ (B, D) CD11b<sup>+</sup>CD11c<sup>+</sup> DCs. Data shown are Mean± SD of 6 independent experiments. Statistical significance is indicated by * p<0.05; **p<0.01 compared with untreated control.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170323, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_E2_and_P4_on_BM_APC_maturation_/3170323", "title"=>"Effects of E2 and P4 on BM APC maturation.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935709"], "description"=>"<p>BM cells isolated from OVX mice (B, C, D) or ER KO mice (A) were cultured with GM-CSF in the presence of 10<sup>-11</sup>M (A) or 10<sup>-9</sup>M E2 (A, B) or (10<sup>-6</sup>M) P4 (C, D). Varying concentrations of E2 inhibitor ICI 182 780 (B), P4 inhibitor RU-486 (C) or Glucocorticoid receptor AL082D06 (D) were used in E2- or P4-treated BM cultures, beginning at the first day of culture. At the end of culture, cells were collected and stained with antibodies against CD11b and CD11c (A, B) and plus MHC II (C, D). Percentage of CD11c+ cells are shown in (A, B) for E2 cultured cells and P4 cultured cells (C, D). Data show Mean ± SD of triplicate determination each time of 3 independent experiments. Statistical significance is indicated by *p<0.05,** p<0.01, ***p<0.001 compared with untreated control.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170398, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_E2_and_P4_on_BM_APC_differentiation_and_maturation_were_mediated_by_their_respective_receptors_/3170398", "title"=>"Effects of E2 and P4 on BM APC differentiation and maturation were mediated by their respective receptors.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935733"], "description"=>"<p>BM cells isolated from OVX mice were cultured with GM-CSF in the presence of E2 (10<sup>-11</sup>M and 10<sup>-9</sup>M) or P4 (10<sup>-8</sup>M and 10<sup>-6</sup>M) or 10<sup>-9</sup>M E2 + 10<sup>-6</sup>M P4 and FITC-Dextran (200μg/ml) was added to the culture on day 5 for further 2 hrs at 37°C. Negative control was FITC-Dextran added to BMDCs and incubated at 4°C for 2 hrs. Cells were collected and stained with antibodies for CD11b and CD11c. Percentage of FITC-Dextran-positive CD11b<sup>+</sup>CD11c<sup>+</sup> DCs were obtained by gating on CD11b<sup>+</sup>CD11c<sup>+</sup> DCs. Representative flow cytometry data are shown in (A) and corresponding data graph are shown in (B). Data shown are Mean ± SD from 4 independent experiments. Statistical significance is indicated by *p<0.05; ** p<0.01; ***p<0.001 compared with untreated control or the comparison of combination treatment with single hormone treatment.</p>", "links"=>[], "tags"=>["differentiation", "hormone", "P 4", "BM precursor cells", "LPS", "CD 11c", "CD 11b", "bone marrow myeloid DCs", "MHC", "E 2 effects", "presence", "murine bone marrow", "function", "Bone Marrow Derived Dendritic Cells", "BMDC", "concentration", "E 2", "High Physiological Concentrations", "IL"], "article_id"=>3170431, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Physiology", "Ecology", "Immunology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Fangming Xiu", "Varun C. Anipindi", "Philip V. Nguyen", "Jeanette Boudreau", "Hong Liang", "Yonghong Wan", "Denis P. Snider", "Charu Kaushic"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153304.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_E2_and_P4_on_the_uptake_of_FITC_Dextran_by_BMDC_/3170431", "title"=>"Effects of E2 and P4 on the uptake of FITC-Dextran by BMDC.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-11 07:49:51"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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