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1.
Korean J Parasitol ; 58(3): 217-227, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32615735

RESUMO

Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.


Assuntos
Adipócitos/imunologia , Macrófagos/imunologia , Neoplasias da Próstata/etiologia , Neoplasias da Próstata/parasitologia , Trichomonas vaginalis , Animais , Comunicação Celular/imunologia , Linhagem Celular Tumoral , Quimiocinas/imunologia , Inflamação , Masculino , Camundongos , Obesidade , Neoplasias da Próstata/patologia , Fatores de Risco
3.
Biochem J ; 477(3): 583-600, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32026949

RESUMO

A central function of adipose tissue is in the management of systemic energy homeostasis that is achieved through the co-ordinated regulation of energy storage and mobilization, adipokine release, and immune functions. With the dramatic increase in the prevalence of obesity and obesity-related metabolic disease over the past 30 years, there has been extensive interest in targeting adipose tissue for therapeutic benefit. However, in order for this goal to be achieved it is essential to establish a comprehensive atlas of adipose tissue cellular composition and define mechanisms of intercellular communication that mediate pathologic and therapeutic responses. While traditional methods, such as fluorescence-activated cell sorting (FACS) and genetic lineage tracing, have greatly advanced the field, these approaches are inherently limited by the choice of markers and the ability to comprehensively identify and characterize dynamic interactions among stromal cells within the tissue microenvironment. Single cell RNA sequencing (scRNAseq) has emerged as a powerful tool for deconvolving cellular heterogeneity and holds promise for understanding the development and plasticity of adipose tissue under normal and pathological conditions. scRNAseq has recently been used to characterize adipose stem cell (ASC) populations and has provided new insights into subpopulations of macrophages that arise during anabolic and catabolic remodeling in white adipose tissue. The current review summarizes recent findings that use this technology to explore adipose tissue heterogeneity and plasticity.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo Branco , Macrófagos/metabolismo , Células Estromais/citologia , Adipócitos/imunologia , Tecido Adiposo/citologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Animais , Comunicação Celular , Citometria de Fluxo , Humanos , Macrófagos/citologia , Obesidade/metabolismo , Obesidade/terapia , Análise de Sequência de RNA , Análise de Célula Única , Células Estromais/metabolismo , Células Estromais/patologia
4.
Proc Natl Acad Sci U S A ; 117(6): 2751-2760, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31980524

RESUMO

Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.


Assuntos
Tecido Adiposo/imunologia , Interleucina-6/imunologia , Obesidade/imunologia , Proteína ADAM10/genética , Proteína ADAM10/imunologia , Proteína ADAM17/genética , Proteína ADAM17/imunologia , Adipócitos/imunologia , Animais , Feminino , Humanos , Interleucina-6/genética , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Musculares/imunologia , Células Mieloides/imunologia , Obesidade/genética , Especificidade da Espécie
5.
Cancer Immunol Immunother ; 69(1): 115-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31802182

RESUMO

Pro-inflammatory cytokines are crucial mediators of cancer development, representing potential targets for cancer therapy. The molecular mechanism of a vital pro-inflammatory cytokine, IL-17A, in cancer progression and its potential use in therapy through influencing fatty acid (FA) metabolism, especially FA uptake of cancer cells, remains unknown. In the present study, we used IL-17A and ovarian cancer (OvCa), a representative of both obesity-related and inflammation-related cancers, to explore the interactions among IL-17A, cancer cells and adipocytes (which can provide FAs). We found that in the presence of palmitic acid (PA), IL-17A could directly increase the cellular uptake of PA, leading to the proliferation of OvCa cells via the IL-17A/IL-17RA/p-STAT3/FABP4 axis rather than via CD36. Moreover, in vivo experiments using an orthotopic implantation model in IL-17A-deficient mice demonstrated that endogenous IL-17A could fuel OvCa growth and metastasis with increased expression of FABP4 and p-STAT3. Furthermore, analysis of clinical specimens supported the above findings. Our data not only provide useful insights into the clinical intervention of the growth and metastasis of the tumors (such as OvCa) that are prone to growth and metastasis in an adipocyte-rich microenvironment (ARM) but also provides new insights into the roles of IL-17A in tumor progression and immunomodulatory therapy of OvCa.


Assuntos
Adipócitos/imunologia , Interleucina-17/metabolismo , Neoplasias Ovarianas/imunologia , Ácido Palmítico/metabolismo , Adipócitos/metabolismo , Animais , Antígenos CD36/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Humanos , Interleucina-17/genética , Interleucina-17/imunologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Ovário/patologia , Fosforilação , Receptores de Interleucina-17/metabolismo , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Microambiente Tumoral/imunologia
6.
Nat Rev Endocrinol ; 16(1): 30-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776456

RESUMO

Neuroimmunology and immunometabolism are burgeoning topics of study, but the intersection of these two fields is scarcely considered. This interplay is particularly prevalent within adipose tissue, where immune cells and the sympathetic nervous system (SNS) have an important role in metabolic homeostasis and pathology, namely in obesity. In the present Review, we first outline the established reciprocal adipose-SNS relationship comprising the neuroendocrine loop facilitated primarily by adipose tissue-derived leptin and SNS-derived noradrenaline. Next, we review the extensive crosstalk between adipocytes and resident innate immune cells as well as the changes that occur in these secretory and signalling pathways in obesity. Finally, we discuss the effect of SNS adrenergic signalling in immune cells and conclude with exciting new research demonstrating an immutable role for SNS-resident macrophages in modulating SNS-adipose crosstalk. We posit that the latter point constitutes the existence of a new field - neuroimmunometabolism.


Assuntos
Adipócitos/imunologia , Adipócitos/metabolismo , Metabolismo Energético/fisiologia , Neuroimunomodulação/fisiologia , Obesidade/imunologia , Obesidade/metabolismo , Animais , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo
7.
Genes Dev ; 33(23-24): 1657-1672, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31727774

RESUMO

In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.


Assuntos
Adipócitos/citologia , Tecido Adiposo/citologia , Tecido Adiposo/imunologia , Morte Celular/fisiologia , Ativação Linfocitária/fisiologia , Células T Matadoras Naturais/fisiologia , Obesidade/fisiopatologia , Células 3T3 , Adipócitos/imunologia , Adipócitos/metabolismo , Animais , Proliferação de Células , Proteína Ligante Fas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptor fas/metabolismo
8.
Mol Med Rep ; 20(4): 3951-3958, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485663

RESUMO

Polygonatum sibiricum polysaccharide (PSP) has been shown to alleviate hyperglycemia and reduce oxidative stress to delay the progression of diabetic retinopathy and cataracts. However, its role and underlying mechanisms in regulating type 2 diabetes mellitus (T2DM) remain unclear. Nuclear factor erythroid 2­related factor 2 (Nrf2) activation plays a protective role in T2DM. The present study focused on the effect of PSP on inflammatory cytokine secretion and Nrf2 expression in the adipocytes of T2DM patients. In this study, high­glucose­ and high­insulin­induced 3T3­L1 adipocytes were used to mimic insulin­resistant (IR)­3T3­L1 adipocytes. Furthermore, the effect and underlying mechanisms of PSP on inflammation and glucose uptake in IR­3T3­L1 adipocytes were investigated. The present study found that proliferation after 50, 100 and 250 µg/ml PSP treatment had no significant change in normal 3T3­L1 adipocytes. A total of 50, 100 and 250 µg/ml of PSP also alleviated IL­1ß, IL­6, and TNF­α levels and promoted proliferation, glucose uptake, and glucose transporter 4 expression in IR­3T3­L1 adipocytes. Furthermore, 50, 100 and 250 µg/ml PSP promoted Nrf2 and HO­1 expression. However, silencing Nrf2 expression reversed the effect of 100 µg/ml PSP in IR­3T3­L1 adipocytes. In conclusion, these results suggest that PSP alleviates inflammatory cytokines and promotes glucose uptake in IR­3T3­L1 adipocytes by promoting Nrf2 expression. PSP may be a potential therapeutic agent for T2DM treatment by promoting Nrf2 expression.


Assuntos
Adipócitos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Citocinas/imunologia , Fator 2 Relacionado a NF-E2/genética , Polissacarídeos/farmacologia , Células 3T3-L1 , Adipócitos/imunologia , Animais , Anti-Inflamatórios/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/imunologia , Hiperinsulinismo/tratamento farmacológico , Hiperinsulinismo/imunologia , Camundongos , Polygonatum/química , Polissacarídeos/química , Regulação para Cima/efeitos dos fármacos
9.
Methods Mol Biol ; 2032: 115-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522416

RESUMO

The human obese subcutaneous adipose tissue (SAT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses, and increased secretion of autoimmune antibodies. Immune cells are recruited to the SAT by chemokines released by both adipocytes and infiltrating immune cells. We describe here the characterization of B lymphocytes from the SAT and blood (control) of obese females undergoing weight reduction surgeries (breast reduction or panniculectomy). We show how to isolate the immune cells from the blood and SAT, how to characterize B cells and their subsets, and how to measure markers of activation and/or transcription factors in SAT-derived B cells and B cell subsets. We also show how to evaluate other immune cell types infiltrating the SAT, including T cells, NK cells, monocyte/macrophages, in order to measure relative proportions of these cell types as compared to the blood.


Assuntos
Autoanticorpos/imunologia , Linfócitos B/imunologia , Imunofenotipagem/métodos , Gordura Subcutânea/imunologia , Adipócitos/imunologia , Autoanticorpos/isolamento & purificação , Humanos , Inflamação/imunologia , Resistência à Insulina/imunologia
10.
Lipids Health Dis ; 18(1): 171, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521168

RESUMO

Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.


Assuntos
Adipócitos/imunologia , Adiponectina/imunologia , Citocinas/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Lectinas/imunologia , Obesidade/imunologia , Psoríase/imunologia , Adipócitos/efeitos dos fármacos , Adipócitos/patologia , Adiponectina/agonistas , Adiponectina/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Citocinas/agonistas , Citocinas/genética , Proteínas Ligadas por GPI/agonistas , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/imunologia , Lectinas/agonistas , Lectinas/genética , Leptina/antagonistas & inibidores , Leptina/genética , Leptina/imunologia , Terapia de Alvo Molecular/métodos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/fisiopatologia , Psoríase/tratamento farmacológico , Psoríase/genética , Psoríase/fisiopatologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
11.
J Agric Food Chem ; 67(30): 8361-8369, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31339708

RESUMO

The calcium-sensing receptor (CaSR), a G-protein receptor, is well recognized for its role in the regulation of adipocyte proliferation, in modulating adipose tissue dysfunction, and as a potential target for therapeutic intervention. In the present study, we investigate the anti-inflammatory effect of γ-glutamylvaline (γ-EV) on mouse adipocytes and explore the role of γ-EV-activated CaSR in the regulation of cellular homeostasis using the mouse 3T3-L1 cell line in vitro model. Our results indicate that the 3T3-L1 adipocyte-like cells accumulated lipids and expressed CaSR after 2 days of differentiation and 7 days of maturation period. The pretreatment with γ-EV (10 µM) suppressed the production of TNF-α-induced pro-inflammatory cytokines, i.e., IL-6 (23.92 ± 5.45 ng/mL, p < 0.05)) and MCP-1 (101.17 ± 39.93 ng/mL, p < 0.05), while enhancing the expression of PPARγ (1.249 ± 0.109, p < 0.001) and adiponectin (7.37 ± 0.59 ng/mL, p < 0.05). Elevated expression of Wnt5a was detected in γ-EV-treated cells (115.90 ± 45.50, p < 0.001), suggesting the involvement of the Wnt/ß-catenin pathway. Also, phosphorylation of ß-catenin was shown to be significantly inhibited (0.442 ± 0.034) by TNF-α but restored when cells were pretreated with γ-EV (0.765 ± 0.048, p < 0.05). These findings suggest that γ-EV-induced CaSR activation not only prevents TNF-α-induced inflammation in adipocytes but also modulates the cross-talk between Wnt and PPARγ pathways. Concentrations of serine phosphorylated IRS-1 were shown to be lower in γ-EV-treated cells, indicating γ-EV may also prevent inflammation in the context of insulin resistance. Thus, γ-EV-activated CaSR plays a significant role in the cross-talk between adipocyte inflammatory and metabolic pathways through the regulation of extracellular sensing.


Assuntos
Adipócitos/efeitos dos fármacos , Dipeptídeos/farmacologia , Receptores de Detecção de Cálcio/imunologia , Células 3T3-L1 , Adipócitos/imunologia , Animais , Interleucina-6/genética , Interleucina-6/imunologia , Camundongos , PPAR gama/genética , PPAR gama/imunologia , Fosforilação , Receptores de Detecção de Cálcio/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
12.
Nat Commun ; 10(1): 3254, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332184

RESUMO

Pathogenic factors driving obesity to type 2 diabetes (T2D) are not fully understood. Group 1 innate lymphoid cells (ILC1s) are effectors of innate immunity and enriched in inflamed tissues. Here we show that the number of adipose ILC1s increases in obese T2D patients and correlates with glycemic parameters and with the number of ILC1s in the blood; circulating ILC1 numbers decrease as a result of metabolic improvements after bariatric surgery. In vitro co-culture experiments show that human adipose ILC1s promote adipose fibrogenesis and CD11c+ macrophage activation. Reconstruction of the adipose ILC1 population in Prkdc-/-IL2rg-/- mice by adoptive transfer drives adipose fibrogenesis through activation of TGFß1 signaling; however, transfer of Ifng-/- ILC1s has no effect on adipose fibrogenesis. Furthermore, inhibiting adipose accumulation of ILC1s using IL-12 neutralizing antibodies attenuates adipose tissue fibrosis and improves glycemic tolerance. Our data present insights into the mechanisms of local immune disturbances in obesity-related T2D.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Imunidade Inata , Linfócitos/metabolismo , Obesidade/metabolismo , Adipócitos/citologia , Adipócitos/imunologia , Adipócitos/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Animais , Cirurgia Bariátrica , Proteína Quinase Ativada por DNA/genética , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Fibrose , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade gama Comum de Receptores de Interleucina/metabolismo , Linfócitos/citologia , Linfócitos/imunologia , Ativação de Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , Obesidade/imunologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31279083

RESUMO

The aim was to study the effect of resveratrol on the interplay of inflammatory signals using three different cell models; a metabolic organ (liver), an endocrine organ (visceral adipose tissue, VAT) and an immune organ (head kidney leukocytes, HKL) following lipopolysaccharide challenge (LPS). Atlantic salmon HKL, liver cells and VAT were isolated from the same fish (n = 5). Each cell type was cultured either as mono-cultures, as co-cultures between HKL-liver cells, liver cells-VAT and HKL-VAT. Triple -cultures included all three tissues. In all cultures of HKL, LPS induced transcription of IL-1ß, cox2, tnfα, IL-12, ccattß and Ahr were significantly inhibited by resveratrol (100, 200 µM). Likewise, in all cultures of liver cells, the LPS induced expression of IL-1ß was inhibited by resveratrol (100 and 200 µM). HKL, both mono-cultures and triple-cultures and VAT cocultured with liver cells, showed LPS induced cox2 transcription that was inhibited by resveratrol (100 and 200 µM). In contrast, VAT cultured as triple cultures, resveratrol 200 µM particularly, in the presence of LPS, seemed to increase the expression of IL-1ß and ccattß. Resveratrol did not significantly affect lox5 expression in any culture. HKL and VAT are the main producers of PGE2 in response to inflammatory stimuli. VAT showed high endogenous production of eicosanoids, particularly LTB4 and LTB5. Resveratrol inhibited bot LPS induced and endogenous eicosanoid production. Possible targets of resveratrol, Sirt1 and pAMPK were affected differently in the different cells and tissue studied.


Assuntos
Adipócitos/efeitos dos fármacos , Rim Cefálico/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Resveratrol/farmacologia , Adipócitos/citologia , Adipócitos/imunologia , Animais , Células Cultivadas , Técnicas de Cocultura/métodos , Eicosanoides/metabolismo , Proteínas de Peixes/metabolismo , Rim Cefálico/citologia , Rim Cefálico/imunologia , Hepatócitos/citologia , Hepatócitos/imunologia , Imunidade/genética , Inflamação/tratamento farmacológico , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/imunologia , Leucócitos/citologia , Leucócitos/imunologia , Lipopolissacarídeos/imunologia , Fígado/citologia , Fígado/imunologia , Salmo salar , Transcrição Genética/efeitos dos fármacos
14.
EBioMedicine ; 46: 387-398, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31327694

RESUMO

BACKGROUND: The bone marrow (BM) is a major reservoir of resting memory T cells and long-lived plasma cells, capable of providing protection against recurrent infections. Whether the age-related accumulation of adipose tissue in the BM affects the functionality and maintenance of memory cells is not well understood. METHODS: For the first time, we compare human femur marrow adipose tissue (fMAT) and subcutaneous white adipose tissue of the thigh (tsWAT) obtained from the same donors. Therefore, we used microarrays for comparative global gene expression analysis, and employed assays to analyse parameters of adipocyte biology, inflammation and oxidative stress. FINDINGS: We show that fMAT adipocytes differ significantly from tsWAT adipocytes regarding specific gene expression profiles including inflammatory responses and adipogenesis/adipocyte phenotype. Concomitant with considerably lower levels of CD36, a membrane-associated protein important for long-chain fatty acid uptake that is used as maturation marker, fMAT adipocytes are smaller and contain less triglycerides. fMAT adipocytes secrete similar levels of adiponectin and leptin as tsWAT adipocytes, and express increased levels of pro-inflammatory molecules concomitant with an elevated generation of reactive oxygen species (ROS) and impaired function of plasma cells in the BM. INTERPRETATION: Our findings suggest that fMAT is a unique type of adipose tissue containing small adipocytes with lower CD36 protein and triglyceride levels than tsWAT but high adipokine secretion. Moreover, fMAT adipocytes secrete high levels of pro-inflammatory cytokines, contributing to inflammation and impairment of plasma cell function in the BM, suggesting that fMAT has more immune regulatory functions than tsWAT.


Assuntos
Adipócitos/imunologia , Adipócitos/metabolismo , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Imunomodulação , Idoso , Biomarcadores , Antígenos CD36/metabolismo , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Imunofluorescência , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
15.
Genes (Basel) ; 10(6)2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234442

RESUMO

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45- fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated.


Assuntos
Túnica Adventícia/imunologia , Cartilagem/metabolismo , Imunofenotipagem , Osteoartrite/tratamento farmacológico , Adipócitos/efeitos dos fármacos , Adipócitos/imunologia , Túnica Adventícia/efeitos dos fármacos , Cartilagem/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Citometria de Fluxo , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Osteoartrite/imunologia , Osteoartrite/metabolismo , Pericitos/efeitos dos fármacos , Pericitos/imunologia
16.
PLoS One ; 14(5): e0217090, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31100089

RESUMO

Chronic inflammation is a fundamental symptom of many diseases. Catechin possesses anti-oxidant and anti-inflammatory properties. However, the mechanism of catechin to prevent inflammation in 3T3-L1 adipocytes caused by TNF-α remains unknown. Therefore, the effects of catechin on the gene expression of cytokines and the activation of cell signals in TNF-α induced 3T3-L1 adipocytes were investigated. The effects of catechin on adipogenesis and cell viability were detected by Oil Red O staining and CCK-8 assay, respectively. The genes expression of cytokines was determined by real-time RT-PCR. The expression of NF-κB, AMPK, FOXO3a and SIRT1 on translation level was determined by western blotting analysis. The results demonstrated that catechin significantly enhanced adipogenesis and cell viability. catechin inhibited the gene expression of pro-inflammatory cytokines including IL-1α, IL-1ß, IL-6, IL-12p35, and inflammatory enzymes including iNOS and COX-2, but enhanced the gene expression of anti-inflammatory cytokines including IL-4 and IL-10. Catechin also inhibited the activation of NF-κB, AMPK, FOXO3a and SIRT1, but increased the phosphorylation level of the above factors. All these results indicated that as a potential therapeutic strategy catechin has the ability of attenuating inflammatory response triggered by TNF-α through signaling cascades involved in inflammation and cytokines.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Catequina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/prevenção & controle , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/toxicidade , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/imunologia , Adipócitos/metabolismo , Adipogenia , Animais , Citocinas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Sirtuína 1/genética
17.
Carcinogenesis ; 40(7): 914-923, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31067318

RESUMO

Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and worse prognosis for PC patients. Recently, we showed in men that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures, was associated with high-grade PC. Possibly, interventions that suppress periprostatic WAT inflammation will improve outcomes for men with PC. Here, we tested the hypothesis that supplemental 17ß-estradiol (E2) could decrease periprostatic WAT inflammation in obese male mice. Mice were fed a high-fat diet to induce periprostatic WAT inflammation before being treated with supplemental E2. E2 supplementation suppressed caloric intake, induced weight loss, decreased periprostatic WAT inflammation and downregulated the expression of genes linked to inflammation including Cd68, Mcp1 and Tnf. Similar to the effects of E2 supplementation, treatment with diethylstilbestrol, a synthetic estrogen, also suppressed caloric intake and reduced periprostatic WAT inflammation. To determine whether the observed effects of supplemental estrogen could be reproduced by caloric restriction (CR) alone, obese mice were put on a 30% CR diet. Like estrogen treatment, CR was effective in reducing body weight, periprostatic WAT inflammation and the expression of pro-inflammatory genes. Transcriptomic analyses of periprostatic fat showed that obesity was associated with enrichment in inflammatory response pathways, which were normalized by both supplemental E2 and CR. Taken together, these findings strengthen the rationale for future efforts to determine whether either CR or supplemental estrogen will decrease periprostatic WAT inflammation and thereby improve outcomes for men with PC.


Assuntos
Restrição Calórica , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Inflamação/terapia , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade/complicações , Adipócitos/imunologia , Adipócitos/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Inflamação/imunologia , Inflamação/patologia , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/patologia , Masculino , Camundongos , Obesidade/imunologia , Obesidade/terapia , Próstata/efeitos dos fármacos , Próstata/imunologia , Próstata/patologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
18.
Autoimmun Rev ; 18(7): 673-678, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059842

RESUMO

BACKGROUND: Thyrocytes secrete CXC chemokines, particularly (C-X-C motif) ligand (CXCL)8 and CXCL10; its physiopathological significance remains unclear. This study investigates the modulation of the secretion of CXCL8 vs. CXCL10, in human primary cells cultures of thyroid follicular cells (TFC) in Graves' disease (GD), and fibroblasts (OF) or preadipocytes (OP) from Graves' ophthalmopathy (GO). METHODS: Cells were initially incubated with different concentrations of tumor necrosis factor (TNF)α (1, 5, 10 ng/mL). Then, CXCL8 and CXCL10 were measured in the supernatants of TFC, OF or OP cells basally and after 24 h of treatment with interferon (IFN)γ (1000 IU/mL) and/or TNFα (10 ng/mL), in presence/absence of the peroxisome proliferator activated receptor (PPAR)γ agonist pioglitazone (0, 0.1, 1, 5, 10, 20 µM), or the PPARα agonist fenofibrate (5, 10, 50, 100 µM). RESULTS: CXCL8, not CXCL10, was detected in basal conditions in TFC, OF and OP. CXCL8 secretion increased dose-dependently with increasing concentrations of TNFα. CXCL10 secretion was significantly stimulated by IFNγ (P < 0.01) and not by TNFα, whereas CXCL8 was induced by TNFα (P < 0.01), and inhibited by IFNγ (P < 0.01) in TFC, OF and OP. Combining TNFα and IFNγ, the IFNγ-induced CXCL10 secretion was synergistically increased (P < 0.01) while the TNFα-induced CXCL8 secretion (P < 0.01) was reversed in all cell types. Pioglitazone had no significant effect on the secretion of CXCL8 stimulated by TNFα, while inhibited CXCL10. Fenofibrate, in presence of IFNγ plus TNFα, dose-dependently inhibited both CXCL10 and CXCL8 release. CONCLUSION: We first show that TFC, OF, and OP secrete CXCL8 and CXCL10 differentially, sustained by specific proinflammatory cytokines or their combination. This could reflect a different role of the two chemokines in the course of the disease, as CXCL10 could be associated with the initial phase of the disease when IFNγ is preponderant, while CXCL8 could be associated with a later chronic phase of the disease, when TNFα prevails.


Assuntos
Adipócitos/imunologia , Citocinas/imunologia , Fibroblastos/imunologia , Doença de Graves/imunologia , Oftalmopatia de Graves/imunologia , PPAR gama/imunologia , Células Epiteliais da Tireoide/imunologia , Células Cultivadas , Humanos
19.
Fish Shellfish Immunol ; 91: 343-349, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31042574

RESUMO

Excessive body fat is a chronic inflammatory disorder. In this process, white adipose tissue (WAT) performs immune activities because of the dysregulated expression of adipokines. Excessive fat is accumulated in farmed fish, thereby threatening fish health. Studies have shown that adipose tissue is also an active immune organ in fish, capable of participating in and influencing immune responses. Adipocytes are the main cellular component of adipose tissue; however, little is known about the relationship between adipocyte and inflammation in fish. In this study, we analyzed transcriptome changes during adipogenesis in the primary culture of grass carp adipocytes using bioinformatics. The results showed that inflammatory signaling pathway may be activated during grass carp adipocyte differentiation, such as NFκB signaling pathway, Toll-like receptor signaling pathway and Adipocytokine signaling pathway, indicating that grass carp adipocytes have immune activities. Exposure to LPS induced expression of adipokines genes in adipocytes and preadipocytes, including NF-kB, IL-6, MCP-1 and TNFα, suggesting that preadipocytes and adipocytes both have immune response and the immune activity is conserved in vertebrates white adipocytes. Further study found that these immune marker genes were higher expressed in adipocytes compared with preadipocytes in LPS-induced inflammation. In summary, adipocyte should be considered as an active immune site in fish. Adipocytes have greater potency compared with preadipocytes in LPS-induced inflammation. This study indicated that adipocytes and preadipocytes may have different contribution in inflammation.


Assuntos
Adipócitos/imunologia , Adipogenia/imunologia , Carpas/imunologia , Imunidade Inata/fisiologia , Lipopolissacarídeos/farmacologia , Adipócitos/metabolismo , Animais
20.
Int Immunol ; 31(11): 729-742, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31094421

RESUMO

Stromal cells in bone marrow (BM) constitute a specific microenvironment supporting the development and maintenance of hematopoietic cells. Adiponectin is a cytokine secreted by adipocytes. Besides its anti-diabetic and anti-atherogenic roles, adiponectin reportedly regulates the development and function of hematopoietic cells in BM. However, it remains unclear whether mesenchymal stromal cells in BM express adiponectin. Here, we show that PDGFRß+VCAM-1+ stromal cells express adiponectin. Lineage tracing revealed that a majority of PDGFRß+VCAM-1+ cells were targeted by an adiponectin promoter-driven Cre (Adipoq-Cre) transgene. Additionally, the Adipoq-Cre transgene targets a minority of osteoblasts at a younger age but larger populations are targeted at an older age. Furthermore, the Adipoq-Cre transgene targets almost all CXCL12-abundant reticular (CAR) cells and most of the stromal cells targeted by the Adipoq-Cre transgene are CAR cells. Finally, deletion of interleukin-7 (IL-7) by the Adipoq-Cre transgene resulted in severe impairment of B lymphopoiesis in BM. These results demonstrate that PDGFRß+VCAM-1+ stromal cells in BM express adiponectin and are targeted by the Adipoq-Cre transgene, suggesting a broader specificity of the Adipoq-Cre transgene.


Assuntos
Adiponectina/biossíntese , Medula Óssea/imunologia , Integrases/genética , Células-Tronco Mesenquimais/imunologia , Regiões Promotoras Genéticas/genética , Transgenes/genética , Adipócitos/imunologia , Animais , Integrases/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/imunologia
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