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M L Batista Jr Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil
Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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R X Neves Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil
Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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S B Peres Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil
Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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A S Yamashita Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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C S Shida Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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S R Farmer Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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M Seelaender Laboratory of Adipose Tissue Biology, Department of Physiological Sciences, Cancer Metabolism Research Group, Department of Biochemistry, Institute of Science and Technology, Center for Integrated Biotechnology, University of Mogi das Cruzes, Avenida Doutor Cândido Xavier de Almeida Souza, 200 Vila Partênio, Mogi das Cruzes, Sao Paulo 08780-911, Brazil

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ATG GTG AGA AAC C-3′ and antisense, 5′-CCC ATG GAT GTA CAG TAG CAG A-3′) and macrophage migration inhibitory factor (MIF; NM 031051.1: sense, 5′-TCC CGG ACC ACG TCA TGA CTT T-3′ and antisense, 5′-CGT TGG CTG CGT TCA TGT CGT AAT-3′) were designed using

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Yun Wang The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA

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Yue Zheng The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA

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Patsy M Nishina The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA

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Jürgen K Naggert The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA

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inflammation, and obesity-associated cardiomyopathy. Obesity-induced inflammation is characterized in part by the infiltration of macrophages and other immune cells into white adipose tissue, and has been observed in both rodents and humans ( Wellen

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Gabriele Wolf
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Nicole Aumann Department of Medical Biochemistry and Molecular Biology, Institute of Community Medicine, Department of Pediatric Hematology and Oncology, UCD School of Biomolecular and Biomedical Science, University of Greifswald, Klinikum, Sauerbruchstrasse, D-17487 Greifswald, Germany

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Marta Michalska
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Antje Bast
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Jürgen Sonnemann Department of Medical Biochemistry and Molecular Biology, Institute of Community Medicine, Department of Pediatric Hematology and Oncology, UCD School of Biomolecular and Biomedical Science, University of Greifswald, Klinikum, Sauerbruchstrasse, D-17487 Greifswald, Germany

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James F Beck Department of Medical Biochemistry and Molecular Biology, Institute of Community Medicine, Department of Pediatric Hematology and Oncology, UCD School of Biomolecular and Biomedical Science, University of Greifswald, Klinikum, Sauerbruchstrasse, D-17487 Greifswald, Germany

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Uwe Lendeckel
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Philip Newsholme Department of Medical Biochemistry and Molecular Biology, Institute of Community Medicine, Department of Pediatric Hematology and Oncology, UCD School of Biomolecular and Biomedical Science, University of Greifswald, Klinikum, Sauerbruchstrasse, D-17487 Greifswald, Germany

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Reinhard Walther
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, an infiltration of pancreatic islets with lymphocytes, macrophages and neutrophil granulocytes releasing various pro-inflammatory cytokines ( Eizirik & Mandrup-Poulsen 2001 ). Chronic exposure to cytokines such as tumour necrosis factor-α (TNF

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Linda Vignozzi Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Annamaria Morelli Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Erica Sarchielli Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Paolo Comeglio Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Sandra Filippi Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Ilaria Cellai Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Elena Maneschi Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Sergio Serni Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Mauro Gacci Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Marco Carini Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Marie-Pierre Piccinni Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Farid Saad Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy
Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Luciano Adorini Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Gabriella B Vannelli Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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Mario Maggi Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy
Sexual Medicine and Andrology Unit, CIRMAR (Centro Interuniversitario di Ricerca sulle basi molecolari della Malattie della Riproduzione), Department of Anatomy, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, Department of Urology, Immunoallergology Unit, Scientific Affairs Men's Healthcare, Gulf Medical University, Intercept Pharmaceuticals Italia Srl, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy

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et al . 2009 ). Briefly, prostate sections were incubated overnight at 4 °C or with the monoclonal mouse anti-CD45 (1:100 vol/vol, DakoCytomation, Copenhagen, Denmark), the anti-macrophage antibody RAM11 (Dako, Carpenteria, CA, USA; 1:80 vol/vol), or

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Amanda E Garza Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Elijah Trefts Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Isis A Katayama Rangel Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Danielle Brooks Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Rene Baudrand Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Department of Endocrinology, School of Medicine, Pontificia Universidad Catolica De Chile, Santiago, Chile

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Burhanuddin Moize Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Jose R Romero Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Sanjay Ranjit Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Thitinan Treesaranuwattana Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Tham M Yao Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Gail K Adler Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Luminita H Pojoga Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Gordon H Williams Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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weight/body weight ratio in any of the four treatment groups or two genotypes ( Table 1 ). As a measure of cardiac injury, as described in the methods section. Macrophage infiltrates and focal adhesions were minimal to not observed in the aldosterone

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Madan L Nagpal
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Yue Chen
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Tu Lin
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variety of compounds that affect Leydig cell function. CXCL10 (cytokine-responsive gene-2) has been shown to be secreted by Leydig cells, macrophages and T cells into the microenvironment of the testis ( Hu et al. 1998 , Goffic et al. 2002 ). CXCL10

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Vincent Ricchiuti
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Christine G Lian
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Eveline M Oestreicher
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Loc Tran
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James R Stone Division of Endocrinology, Department of Pathology, Diabetes and Hypertension, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115, USA

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Tham Yao
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Ellen W Seely
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Gordon H Williams
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Gail K Adler
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), the chemokine osteopontin (OPN), and ED-1 (a protein expressed by monocytes/macrophages)). The cardiac levels of PAI-1 protein were increased in rats receiving E 2 when compared with those not receiving E 2 ( Fig. 6 A, P <0.01). Furthermore, E 2

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MS Gregory
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LA Duffner
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DE Faunce
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EJ Kovacs
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Previous studies in our laboratory have demonstrated that cell-mediated immune function was suppressed in female, but not male, mice at 10 days after burn injury and was mediated, in part, by increased production of interleukin-6 (IL-6). Because 17beta-estradiol (E(2)) influences immune function after trauma and the hormone is known to regulate IL-6 production, the effect of E(2) on immune function after thermal injury was examined. Increased circulating concentrations of E(2) corresponded with suppressed delayed-type hypersensitivity (DTH) and splenocyte-proliferative responses, and increased circulating concentrations of IL-6 in female mice after burn. Ovariectomy restored the suppressed DTH response and decreased IL-6 concentrations, and administration of exogenous E(2) to both ovariectomized females and intact male mice resulted in a suppressed DTH response. In addition, in vitro treatment with E(2) suppressed splenocyte proliferation in a macrophage-dependent manner and enhanced macrophage production of IL-6. These results strongly suggest that the sex difference in cell-mediated immunity 10 days after burn injury is mediated by altered concentrations of E(2), which in turn modulate key macrophage-derived immunoregulatory cytokines.

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Christianne M A Reijnders Departments of Endocrinology and
Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, brug 124, PO Box 7057, 1081 HV Amsterdam, The Netherlands

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Nathalie Bravenboer Departments of Endocrinology and
Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, brug 124, PO Box 7057, 1081 HV Amsterdam, The Netherlands

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Annechien M Tromp Departments of Endocrinology and
Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, brug 124, PO Box 7057, 1081 HV Amsterdam, The Netherlands

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Marinus A Blankenstein Departments of Endocrinology and
Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, brug 124, PO Box 7057, 1081 HV Amsterdam, The Netherlands

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Paul Lips Departments of Endocrinology and
Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, brug 124, PO Box 7057, 1081 HV Amsterdam, The Netherlands

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) did not express IGF-I mRNA. IGF-I mRNA was expressed in the intracortical endothelial cells of blood vessels (Fig. 4F ) and in the periosteum of control tibiae (data not shown). Some cells of the bone marrow i.e. megakaryocytes, macrophages, and

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CP Sewter
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JE Digby
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F Blows
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J Prins
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S O'Rahilly
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Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.

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