?rea de concentra??o: Neuroimunoendocrinologia. / Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2016-01-04T18:24:18Z No. of bitstreams: 2 wellington_fabiano_gomes.pdf: 3823362 bytes, checksum: 39e0250b96c5bd95724cca2eef404fd7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2016-01-04T18:24:49Z (GMT) No. of bitstreams: 2 wellington_fabiano_gomes.pdf: 3823362 bytes, checksum: 39e0250b96c5bd95724cca2eef404fd7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-01-04T18:24:49Z (GMT). No. of bitstreams: 2 wellington_fabiano_gomes.pdf: 3823362 bytes, checksum: 39e0250b96c5bd95724cca2eef404fd7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2014 / Funda??o de Amparo ? Pesquisa do estado de Minas Gerais (FAPEMIG) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Capes) / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / A osteartrite de joelho (OAj) ? uma doen?a que afeta principalmente os idosos e pode levar a grandes limita??es f?sicas e funcionais. No entanto, os efeitos espec?ficos da terapia por exerc?cios, especialmente a caminhada sobre o sistema imunol?gico, s?o desconhecidas. Portanto, este estudo teve como objetivo analisar o efeito de 12 semanas de caminhada (3x / semana) no perfil de leuc?citos, nos n?veis plasm?ticos de interleucina (IL-6), do fator de necrose tumoral alfa (TNF-?), dos receptores sol?veis de TNF-? (sTNFR1 e sTNFR2), e do fator neurotr?fico derivado do c?rebro (BDNF) a partir de plasma retirado do sangue perif?rico de mulheres idosas com OAj. Al?m disso, as avalia??es cl?nicas e funcionais (teste de WOMAC, teste de caminhada de 6 minutos, SF-36, a percep??o da dor) foram realizadas. Dezesseis mulheres (idade: 67 ? 4 anos, ?ndice de massa corporal: 28,07 ? 4,16 kg/m2) participaram de um programa de caminhada (36 sess?es de fisioterapia) e de um esfor?o f?sico (01 sess?o de fisioterapia). As vari?veis foram avaliadas antes e ap?s 12 semanas de treinamento com dura??o (30-55 min) e intensidade (70-80% da FCm?x) progressivamente maiores. As amostras de sangue coletadas foram analisadas com um contador de c?lulas, cit?metro de fluxo e pelo m?todo ELISA. As sess?es de fisioterapia resultaram em um aumento de 47% da qualidade de vida (p <0,05) e um aumento de 21% no VO2max (p <0,0001) em mulheres idosas com OAj. Al?m disso, houve uma redu??o nas c?lulas T CD4 + (antes 46,59 ? 7%, depois 44,58 ? 9%, p = 0,0189) e uma intensidade de fluoresc?ncia mais elevada para CD18 + CD4 + (antes 45,30 ? 10, depois de 64,27 ? 33, p = 0,0256) e CD18 + CD8 + (antes: 64,2 ? 27, depois de 85,02 ? 35, p = 0,0130). A ET aumentou a concentra??o plasm?tica de sTNR1; no entanto, diminuiu a concentra??o de plasma de sTNFR2, quando comparado com os n?veis em repouso de pacientes. O exerc?cio agudo afetou diferencialmente os n?veis de sTNFR1 dependente de quando as amostras foram tomadas, antes e ap?s o treinamento aer?bico. No entanto, os n?veis de sTNFR2 n?o foram afetados pelo treinamento. O exerc?cio agudo aumentou os n?veis de BDNF apenas antes do per?odo de treinamento de 12 semanas (p <0,001). Al?m disso, houve aumento das concentra??es plasm?ticas de BDNF (p <0,0001) e melhora em par?metros cl?nicos (funcional p <0,001; percep??o da dor p <0,01). A varia??o dos n?veis de receptores sol?veis correlacionou-se com a melhora funcional; no entanto, os marcadores inflamat?rios de osteoartrite (IL-6 e TNF-?) n?o foram afetados pelas 36 sess?es de fisioterapia. / Tese (Doutorado) ? Programa Multic?ntrico de P?s-Gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2014. / ABSTRACT Osteoarthritis of the knee (kOA) is a disease that mainly affects the elderly and can lead to major physical and functional limitations. However, the specific effects of exercise therapy (ET), specially walking and particularly on the immune system, are unknown. Therefore, this study aimed to analyze the effect of 12 weeks of walking (3x/week) on the leukocyte profile, levels of interleukin 6 (IL-6), tumor necrosis factor alpha, (TNF-?), soluble forms of the TNF-? receptor (sTNFR1 and sTNFR2), and brain-derived neurotrophic factor (BDNF) from plasma taken from the peripheral blood of elderly women with kOA. Additionally, clinical and functional assessments (WOMAC test, 6-min walk, SF-36, pain perception) were performed. Sixteen women (age: 67 ? 4 years, body mass index: 28.07 ? 4.16 kg/m2) participated in a walking program and physical exertion. The variables were assessed before and after 12 weeks of training with a progressively longer duration (30-55 min) and higher intensity (70-80% of HRmax). The blood samples were collected for analysis with a cell counter, the Scan Fac flow cytometer and were measured by ELISA. The ET resulted in a 47% enhancement of the self-reported quality of life (p <0.05) and a 21% increase in the VO2max (p <0.0001) in elderly women with kOA. Furthermore, there was a reduction in CD4+ cells (before 46.59?7%, after 44.58?9%, p=0.0189) and a higher fluorescence intensity for CD18+CD4+ (before 45.30 ? 10, after 64.27 ? 33, p=0.0256) and CD18+CD8+ (before: 64.2 ?27, after 85.02 ?35, p=0.0130). Aerobic training increased the plasma concentration of sTNR1; however, it decreased the plasma concentration of sTNFR2, when compared with levels of resting patients. Acute exercise differentially affects the levels of sTNFR1 dependent on when the samples were taken, before and after aerobic training. However, the levels of sTNFR2 were not affected by training. The acute exercise increased the levels of BDNF only before the 12-week training period (p<0.001). Moreover, the training augmented the plasma concentrations of BDNF (p<0.0001) and improved clinical parameters (functional p<0.001; pain perception p<0.01). The variation in the levels of soluble receptors correlated with functional improvement; however, the inflammatory osteoarthritis markers (IL-6 and TNF-?) were unaffected by the walking exercises, in physical therapy.

INTRODUCTION: Endometriosis is a disease characterized by the presence of extrauterine endometrial implants. Its etiopathogenesis isn’t fully understood, it’s believed that immunological and hormonal factors influence the peritoneal environment, preventing the elimination of refluxed endometrial cells during the menstrual period. In addition, endometriosis has been reported as an inflammatory process and some studies have demonstrated the inflammatory resolutive mediators involvement in endometrial physiology and suggest that they may be involved in the endometriosis progression by anti-inflammatory and antiangeogenic action. OBJECTIVE: To characterize Annexin A1 (ANXA1), FPR2/ALX and cytokines expression in peritoneal endometriosis and to clarify their role in its etiology. METHODS: A laboratory analysis was performed human samples with forty women in reproductive age (22 patients with endometriosis and 18 control women) that had undergone laparoscopic surgery. Peritoneal biopsy e fluid aspirations from endometriosis and control samples were analyzed for the expression of ANXA1, FPR2/ALX and cytokines. ANXA1 and FPR2 / ALX levels were measured by Western blotting and interleukin 1ß (IL-1ß), 4 (IL-4), 6 (IL-6) e 10 (IL-10) were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: The present study identified the presence in human peritoneal tissue of ANXA1 and FPR2 / ALX both in healthy condition and in women with peritoneal endometriosis, however, was lower in endometriosis samples than in control samples. By quantifying the IL-6 and IL-1β cytokines in the peritoneal fluid by ELISA, this study identified a higher IL-6 concentration in endometriosis group, but no significative difference in IL-1ß levels. In all samples, levels of IL-4 and IL-10 cytokines were below the detection level of the method used. CONCLUSION: These results indicate that the reduction of the inflammatory resolution mediators may be responsible for the inflammatory process perpetuation, maintenance and worsening of endometriosis. / Submitted by Lia Karina Volpato (lia.volpato@unisul.br) on 2018-03-13T15:25:32Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação Lia Karina Volpato.pdf: 23378759 bytes, checksum: c029f98522ccc30394074d42329f7c3b (MD5) / Approved for entry into archive by Caroline Correa da Cruz (caroline.cruz@unisul.br) on 2018-03-13T18:35:21Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação Lia Karina Volpato.pdf: 23378759 bytes, checksum: c029f98522ccc30394074d42329f7c3b (MD5) / Made available in DSpace on 2018-03-13T18:35:21Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação Lia Karina Volpato.pdf: 23378759 bytes, checksum: c029f98522ccc30394074d42329f7c3b (MD5) Previous issue date: 2017 / Endometriose é uma doença caracterizada pela presença de implantes endometriais extrauterinos. Sua etiopatogenia não está totalmente esclarecida, acredita-se que fatores imunológicos e hormonais influenciam o ambiente peritoneal, impedindo a eliminação das células endometriais refluídas durante o período menstrual. Além disso, a endometriose tem sido relacionada como um processo inflamatório e alguns estudos têm demonstrado o envolvimento de mediadores pró-resolutivos da inflamação na fisiologia endometrial e sugerem que possam estar envolvidos na progressão da endometriose por ação anti-inflamatória e antiangeogênica. OBJETIVO: Caracterizar a densidade de anexina A1 (ANXA1), FPR2 / ALX e citocinas na endometriose peritoneal e esclarecer seu papel etiológico. MÉTODOS: Foi realizado um estudo de análise laboratorial com amostras humanas de quarenta mulheres em idade reprodutiva (22 pacientes com endometriose e 18 mulheres controle) submetidas à cirurgia laparoscópica. Foram realizadas biópsia peritoneal e aspiração de fluido peritoneal em amostras de endometriose e de controle, que foram analisadas quanto à densidade de ANXA1, FPR2 / ALX e citocinas. Os níveis de ANXA1 e FPR2 / ALX foram medidos por Western blott e as interleucinas 1ß (IL-1ß), 4 (IL-4), 6 (IL-6) e 10 (IL-10) foram quantificadas por ensaio de imunoabsorção enzimática (ELISA). RESULTADOS: O presente estudo identificou a presença no tecido peritoneal humano de ANXA1 e FPR2 / ALX em condições saudáveis e em mulheres com endometriose peritoneal, no entanto, a densidade foi menor nas amostras de endometriose do que nas amostras de controle. Este estudo identificou uma maior concentração de IL-6 no fluido peritoneal do grupo com endometriose, mas não houve diferença significativa nos níveis de IL-1β. Em todas as amostras, os níveis de citocinas IL- 4 e IL- 10 estiveram abaixo do nível de detecção do método utilizado. CONCLUSÃO: Estes resultados indicam que a redução dos mediadores de resolução inflamatória pode ser responsável pela perpetuação, manutenção e agravamento do processo inflamatório da endometriose.

Submitted by Israel Vieira Neto (israel.vieiraneto@ufpe.br) on 2015-03-05T18:31:18Z No. of bitstreams: 2 Dissertação sergio ferreira.pdf: 495221 bytes, checksum: 34587eb69a01f6ac2b83ff92569f588d (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-05T18:31:18Z (GMT). No. of bitstreams: 2 Dissertação sergio ferreira.pdf: 495221 bytes, checksum: 34587eb69a01f6ac2b83ff92569f588d (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2012 / CAPES, CNPq / O câncer cervical (CC) é o segundo tipo de câncer mais comum a afetar mulheres em todo mundo. O Papillomavírus humano (HPV) é encontrado em 99% dos casos de CC e a infecção por esse vírus é considerado um fator de risco para o desenvolvimento do câncer. Muitos estudos tem demonstrado uma relação entre polimorfismos nos genes de citocinas e doenças infecciosas. Polimorfismos nos genes da Interleucina-6 (IL-6) e o Fator de Crescimento Transformador (TGF) β1, importantes mediadores do sistema imunológico, tem sido associados com níveis séricos elevados destas citocinas e no desenvolvimento de muitas doenças e tipos de cânceres. O objetivo desse estudo foi verificar se o SNP -174G/C do gene da IL-6 e T869C e G915C do gene do TGF-β1 estão relacionados com o desenvolvimento de Neoplasias Intraepiteliais Cervicais (NIC). 115 amostras de pacientes saudáveis e 115 de pacientes com lesões foram analisadas. As análises dos SNP foram realizadas através do sequenciamento automático de DNA utilizando o “MEGABACE 1000”. Os genótipos do polimorfismo -174G/C da IL-6 que possuem pelo menos um alelo C parecem estar envolvidos no desenvolvimento de NIC induzida pelo HPV (p=0.05232). Nenhuma diferença significativa foi encontrada entre as frequências alélicas e genotípicas dos polimorfismos da TGF-β1 nos dois grupos analisados. Além disso, polimorfismos nos genes da IL-6 e TGF-β1 não estão envolvidos na progressão do CIN. Este estudo sugere que o polimorfismo -174G/C do gene da IL-6 pode ser usado como um gene marcador da susceptibilidade a infecção pelo HPV, mas não como um marcador de progressão de NIC na população Pernambucana.

L’hépatite B est une maladie infectieuse grave et extrêmement contagieuse. Malgré l’existence d’un vaccin efficace plus de 240 millions de personnes souffrent d’une infection hépatique chronique et plus de 780 000 personnes meurent chaque année des conséquences aiguës ou chroniques de l’hépatite B. Les traitements actuels qui consistent en l’utilisation d’interféron et/ou d’inhibiteurs de la réplication virale sont encore insuffisants. De nouvelles thérapeutiques ciblant l’entrée virale sont en développement, notamment le Myrcludex B qui inhibe l’infection en empêchant l’entrée virale. Cependant, les mécanismes d’entrée du VHB dans l’hépatocyte sont encore mal connus. Récemment, l’identification du NTCP comme récepteur spécifique du VHB a permis de mieux comprendre le mécanisme d’attachement de ce virus. Ce récepteur constitue une nouvelle cible pour des antiviraux. C’est aussi un transporteur de sels biliaires fortement régulé par les cytokines pro-inflammatoires. Les objectifs de ce travail étaient : (i) d’étudier la fusion du VHB, étape cruciale de l’entrée d’un virus enveloppé, en établissant un modèle artificiel de fusion entre des particules virales purifiées et des liposomes, et (ii) d’étudier l’effet de l’interleukine 6 sur l’entrée virale. Nous n’avons pas pu mettre en évidence de fusion entre les particules virales et des liposomes suggérant l’incapacité de ce virus à fusionner avec une bicouche lipidique néanmoins il reste possible que des conditions particulières liées aux spécificités du VHB soient requises. Nos résultats ont également montré que l’interleukine 6 inhibait l’entrée virale en diminuant l’expression de NTCP. / Hepatitis B is a severe and extremely contagious infectious disease. Despite an effective vaccine more than 240 million people are suffering from chronic infection and over 780 000 persons die each year from the consequences of acute and chronic hepatitis B. Current treatments consisting in the use of interferon and/or viral replication inhibitors are insufficient. New therapeutics targeting viral entry are in progress, such as Myrcludex B that has been shown to inhibit HBV infection by preventing HBV entry. However, the mechanism of HBV entry into hepatocytes is still poorly understood. Recently, the identification of NTCP as a specific HBV receptor allowed us to better understand the attachment of this virus. This receptor is now a target for antiviral molecules. It is also a carrier for bile salts known to be strongly regulated by pro inflammatory cytokines. The aims of our thesis were: (i) to study HBV entry by establishing an artificial model of fusion between purified viral particles and liposomes, and (ii) to study the interleukin 6 effect on viral entry. Our results with fusion assays suggest an absence of fusion in the entry process of this virus. However, fusion could require peculiar conditions related to HBV specificities. Our results also demonstrated that interleukin 6 inhibits virus entry by down-regulating NTCP expression.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22147号 / 医博第4538号 / 新制||医||1039(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 濵﨑 洋子, 教授 竹内 理, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Phthalates are industrial chemicals added to plastics found in products such as children’s toys, cosmetics, and household items, and some laboratory studies suggest phthalates may increase levels of inflammation. Chronic inflammation is associated with many chronic health conditions, such as diabetes and rheumatoid arthritis. Although research is limited, recent studies suggest a strong positive relationship between mono-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), and monocarboxynonyl phthalate (MCNP) and c-reactive protein (CRP), as well as monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and interleukin-6 (IL-6). Additionally, this relationship has not been examined among postmenopausal women, a population that is at higher risk of developing chronic health conditions. Our aim was to examine the association between urinary phthalate biomarkers and inflammation biomarkers among postmenopausal women using baseline data from a subset of participants of the Women’s Health Initiative (WHI) (n=443). Phthalate exposure was assessed using phthalate biomarkers (i.e. phthalate metabolites or their molar sum) from urine samples collected at WHI clinical centers from 1993-1998. We measured 13 phthalate metabolites: MEP, MBP, mono-hydroxybutyl phthalate (MHBP), MiBP, mono-hydroxyisobutyl phthalate (MHiBP), monobenzyl phthalate (MBzP), MCPP, mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-carboxyoctyl phthalate (MCOP), and MCNP. Serum and plasma inflammatory biomarker levels (i.e. CRP, IL-6) were measured in separate WHI ancillary studies, using blood samples collected at baseline. We used multivariable linear regression to analyze associations between each phthalate biomarker and inflammation biomarker, adjusting for important covariates. Phthalate biomarkers MCNP (Model 1: b = 0.523; Model 2: b = 0.362) and MCOP (Model 1: b = 0.384; Model 2: b = 0.240) were positively associated with CRP. Additionally, MCNP (Model 1: b = 0.369; Model 2: b = 0.181) was positively associated with IL-6. Statistically significant associations were not observed among the remaining phthalate biomarkers. Our findings suggest that certain phthalates may be related to increasing levels of inflammation.

Maternal immune activation (MIA) can affect fetal brain development and thus behavior of young and adult offspring. Reports have shown that increased Interleukin-6 (IL-6) in the maternal serum plays a key role in altering fetal brain development, and may impair social behaviors in the offspring. Interestingly, these effects could be attenuated by blocking IL-6. The current study investigated the effects of luteolin, a citrus bioflavonoid, and its structural analog, diosmin, on IL-6 induced JAK2/STAT3 (Janus tyrosine kinase-2/signal transducer and activator of transcription-3) phosphorylation and signaling as well as behavioral phenotypes of MIA offspring. Luteolin and diosmin inhibited neuronal JAK2/STAT3 phosphorylation both in vitro and in vivo following IL-6 challenge as well as significantly diminishing behavioral deficits in social interaction. Importantly, our results showed that diosmin (10 mg/kg day) was able to block the STAT3 signal pathway; significantly opposing MIA-induced abnormal behavior and neuropathological abnormalities in MIA/adult offspring. Diosmin's molecular inhibition of JAK2/STAT3 pathway may underlie the attenuation of abnormal social interaction in IL-6/MIA adult offspring.

We defined how blood-derived vitronectin (VTN) rapidly and potently activates leukemia inhibitory factor (LIF) and pro-inflammatory interleukin 6 (IL-6) in vitro and after vascular injury in the brain. Treatment with VTN (but not fibrinogen, fibronectin, laminin-111 or collagen-I) substantially increased LIF and IL-6 within 4 h in C6-astroglioma cells, while VTN-/- mouse plasma was less effective than that from wild-type mice. LIF and IL-6 were induced by intracerebral injection of recombinant human (rh)VTN in mice, but induction seen upon intracerebral hemorrhage was less in VTN-/- mice than in wild-type littermates. In vitro, VTNeffects were inhibited by RGD, αvβ3 and αvβ5 integrin-blocking peptides and antibodies. VTN activated focal adhesion kinase (FAK; also known as PTK2), whereas pharmacological- or siRNA-mediated inhibition of FAK, but not PYK2, reduced the expression of LIF and IL-6 in C6 and endothelial cells and after traumatic cell injury.Dominant-negative FAK (Y397F) reduced the amount of injury-induced LIF and IL-6. Pharmacological inhibition or knockdown of uPAR (also known as PLAUR), which binds VTN, also reduced cytokine expression, possibly through a common target of uPAR and integrins. We propose that VTN leakage into tissues promotes inflammation. Integrin-FAKsignaling is therefore a novel IL-6 and LIF regulation mechanism relevant to the inflammation and stem cell fields.

No description available.

Iron plays a crucial role in various essential functions within the human body, participating in processes vital for overall health and well-being. To address iron deficiency, a wide array of iron supplements are commonly employed. However, it is important to recognize that certain types of iron supplements can have adverse effects on the body, including the induction of oxidative stress and inflammation. Therefore, extensive research is imperative to investigate the inflammatory potential of different sources of iron supplements in order to ensure their safety and effectiveness. In the pursuit of evaluating the inflammatory effects of various iron supplements, researchers frequently employ the Caco2 cell model. In this study, the focus was placed on examining the pro-inflammatory potential of different iron supplements by measuring the levels of a specific inflammatory biomarker, the cytokine IL-6, in the Caco2 cells. To mimic the physiological conditions, the supplements were subjected to a simulated gastrointestinal digestion protocol, ensuring that the Caco2 cells were exposed to digested forms of the supplement after which the levels of IL-6 were determined using ELISA. Surprisingly, the results of the study unveiled intriguing findings. Specifically, the two iron supplements derived from bovine sources exhibited no significant effect on IL-6 levels, indicating a lack of pro-inflammatory activity. However, it was the iron supplement derived from Spirulina, a marine-originated source that captured attention. This particular supplement showcased the ability to decrease the levels of IL-6, suggesting a potentially anti-inflammatory effect on intestinal cells. / <p>Utbytesstudent</p>