Browsing by Subject "Cytokine"
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- PublicationOpen AccessAcidophilic granulocytes of the marine fish gilthead seabream (Sparus aurata L.) produce interleukin-1b following infection with Vibrio anguillarum(Springer, 2004) Chaves-Pozo, Elena; Pelegrin, Pablo; García-Castillo, Jesús; Meseguer, José; García Ayala, Alfonsa; Mulero Méndez, Victoriano Francisco; Bioquímica y Biología Molecular B e InmunologíaThe fish immune response to Gram-negative bacteria is poorly understood. In this study, we use a monoclonal antibody (mAb) specific to acidophilic granulocytes from the marine fish gilthead seabream (Sparus aurata L.), together with an antiserum specific to interleukin-1b (IL-1b) from this species, in order to investigate whether these cells are involved in the immune response against the pathogenic bacterium Vibrio anguillarum and, in particular, in the production of the pro-inflammatory cytokine IL-1b. We found that gilthead seabream head- kidney, peritoneal exudate and peripheral blood leukocytes accumulated proIL-1b intracellularly when challenged in vitro with V. anguillarum, whereas only peritoneal exudate and blood leukocytes were able to accumulate proIL-1b following infection. Importantly, the blood leukocytes from infected animals that accumulated proIL-1b were shown to be the acidophilic granulocytes. A rapid mobilization of such cells from the head-kidney to the site of inflammation following infection with V. anguillarum was also observed.
- ItemOpen AccessAmygdalin improves ovarian function by inhibiting oxidative stress and inflammation in premature ovarian failure mice(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Jintao Han; Jianyuan Li; Jin Yao; Wenwei Jiang; Biología Celular e HistologíaBackground. Menstrual stoppage, follicular dysplasia, and hypergonadotropic hypoestrogenism in women under forty are among the symptoms of premature ovarian failure (POF). This study aimed to explore the role and mechanism of amygdalin on ovarian function in a POF mouse model. Methods. A POF mouse model was established via injection of D-galactose (D-gal), followed by amygdalin treatment. Histological staining of ovarian tissues was applied to determine follicular development and granulosa cell apoptosis. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) were measured in ovarian tissues. Enzyme-linked immunosorbent assay was used to detect levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), anti-Müllerian hormone (AMH), and reactive oxygen species (ROS) in serum, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 levels in ovaries. Results. D-gal increased levels of FSH, LH, ROS, MDA, TNF-α, IL-1β, IL-6, Bax, atretic follicles, and granulosa cell apoptosis, and decreased P, E2, AMH, SOD, GSH-px, Bcl-2, and primordial, primary, secondary, and total follicles (p<0.01). Amygdalin with different concentrations reversed the effects of D-gal on mice (p<0.05). Conclusion. Amygdalin improved ovarian function in POF mice through inhibiting oxidative stress, inflammation, and granulosa cell apoptosis. These results suggested that amygdalin may be a potential antioxidant for POF treatment.
- PublicationOpen AccessCytokine production by newborns: influence of sex and season of birth(Natureportfolio, 2022-08-09) García-Serna, Azahara M; Morales, Eva; Cantero-Cano, Ester; Norte-Muñoz, María; Gil-Buendía, M. Ángeles; Velázquez-Marín, Josefa; Pérez-Fernández, Virginia; Martínez-Torres, Antonia E; García-Marcos, Luis; Hernández Caselles, Trinidad; Martín-Orozco Santiago, María Elena; Bioquímica y Biología Molecular B e InmunologíaBackground: Immune signatures at birth could be associated with clinical outcomes and will improve our understanding of immunity prenatal programming. Methods: Data come from 235 newborns from the cohort study NELA. Production of cytokines was determined using Luminex technology. Associations between cytokine concentrations with sex and season of birth were examined by multivariate regression models. Results: Umbilical cord blood cells produced high levels of inflammatory cytokines, moderate levels of Th1/Th2/Tr-related cytokines, and low levels of Th17 cytokines. Compared to females, male newborn cells secreted higher levels of Th2 (peptidoglycan-stimulated IL-13, odds ratio [OR] = 2.26; 95% CI 1.18, 4.31, p value = 0.013) and Th17 (polyinosinic:polycytidylic acid-stimulated IL-23, OR = 1.82, 95% CI 1.01, 3.27, p value = 0.046) and lower levels of Th1 (olive-stimulated IL-2, OR = 0.56, 95% CI 0.31, 0.99, p value = 0.047) cytokines. Also, children born during warm seasons showed decreased innate cytokine response to peptidoglycan (IL-6, OR = 0.28, 95% CI 0.15, 0.52, p value < 0.001) compared to those born in cold seasons; meanwhile, adaptive immunity cytokines were more frequently secreted by children born during warm seasons in response to allergen extracts (IL-10, OR = 2.11, 95% CI 1.12, 3.96, p value = 0.020; IL-17F, OR = 3.31, 95% CI 1.83, 5.99, p value < 0.001). Conclusion: Newborns showed specific cytokines signatures influenced by sex and season of birth. Impact: There is a limited number of population-based studies on the immune status at birth and the influence of prenatal and perinatal factors on it. Characterization of cytokine signatures at birth related to the prenatal environment could improve our understanding of immunity prenatal programming. Newborns exhibit specific unstimulated and stimulated cytokine signatures influenced by sex and season of birth. Unstimulated and stimulated cytokine signatures in newborns may be associated with the development of related clinical outcomes later in life.
- PublicationOpen AccessDevelopment of an Acrylate Derivative Targeting the NLRP3 Inflam- masome for the Treatment of Inflammatory Bowel Disease(ACS Publications, 2017) Cocco, Mattia; Pellegrini, Carolina; Martínez-Banaclocha, Helios; Giorgis, Marta; Marini, Elisabetta; Costale, Annalisa; Miglio, Gianluca; Fornai, Matteo; Antonioli, Luca; López-Castejón, Gloria; Angosto, Diego; Hafner-Bratkovic, Iva; Regazzoni, Luca; Blandizzi, Corrado; Pelegrin, Pablo; Bertinaria, Massimo; Tapia Abellán, Ana; Bioquímica y Biología Molecular B e InmunologíaPharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of Inflamma- tory Bowel Disease (IBD). In this work, we report the design, the synthesis, and the biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a stable, non toxic compound inhibiting interleukin 1β release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 acti- vation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of DNBS-induced colitis in rats after oral administration.
- PublicationOpen AccessICAM-1 expression on endothelium and systemic cytokine production in cutaneous neutrophilic leukocytoclastic vasculitis in NZBxNZWF1 mice(Murcia : F. Hernández, 2005) Hayashi, T.; Hasegawa, K.; Ichinohe, N.The present study has examined relationship between cutaneous microvessel injury and adhesion molecule expression on the endothelium by cytokines in NZBxNZWF1 (B/WF1) mice, a model for human systemic lupus erythematosus. In advanced ages associated with overt clinical manifestation, but not in early ages, neutrophils with a minor proportion of monocytes and lymphocytes mainly adhered to the endothelium of capillary and the venule with fragmentation (leukocytoclasis), leading to the vascular injury (leukocytoclastic vasculitis). This was confirmed by the leak of monstral blue from the blood vessel. At this stage LFA-1+ leukocytes adhered to intensely expressed ICAM-1 on the endothelium, and this was paralleled with a significant rise in IL-1a and TNF-a in the circulation. The present study suggests that IL-1a and TNF-a may, at least in part, be responsible for the increased ICAM-1 expression on endothelium in cutaneous microvessels, resulting in the vascular injury characterized by neutrophilic leukocytoclasis in B/WF1 mice.
- PublicationOpen AccessInterleukin-6: a molecule with complex biological impact in cancer(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Lacina, Lukáš; Brábek, Jan; Král, Vladimír; Kodet, Ondřej; Smetana Jr, KarelInterleukin-6 is a multifaceted cytokine, usually reported as a pro-inflammatory molecule. However, certain anti-inflammatory activities were also attributed to IL-6. The levels of IL-6 in serum as well as in other biological fluids are elevated in an agedependent manner. Notably, it is consistently reported also as a key feature of the senescence-associated secretory phenotype. In the elderly, this cytokine participates in the initiation of catabolism resulting in, e.g. sarcopenia. It can cross the blood-brain barrier, and so it is in causal association with, e.g. depression, bipolar disorder, schizophrenia, and anorexia. In the cancer patient, IL-6 is produced by cancer and stromal cells and actively participates in their crosstalk. IL-6 supports tumour growth and metastasising in terminal patients, and it significantly engages in cancer cachexia (including anorexia) and depression associated with malignancy. The pharmacological treatment impairing IL-6 signalling represents a potential mechanism of antitumour therapy targeting cancer growth, metastatic spread, metabolic deterioration and terminal cachexia in patients.
- PublicationOpen AccessLectin activities of cytokines and growth factors: function and implications for pathology(Murcia : F. Hernández, 1996) Zanetta, J.P.; Scior, T.; Wantyghem, J.; Wermuth, C.; Aubery, M.; Strecker, G.; Michalski, J.C.The discovery that certain cytokines have carbohydrate-binding (lectin) properties opens new concepts in the understanding of their mechanism of action. The carbohydrate-recognition domain, which is localized opposite to the receptor-binding domain, makes these molecules bi-functional. The expression of the biological activity of the cytokine relies on its carbohydrate-binding activity which allows the association of the cytokine receptor with molecular complexes comprising the specific kinase involved in receptor phosphorylation and in specific signal transduction. It is expected that blood accumulation of free or membrane-bound glycan ligands of cytokines may dramatically perturb their endogenous function inducing specific immunodeficiencies.
PublicationRestrictedMicafungin enhances the human macrophage response to Candida albicans through β-glucan exposure(American Society for Microbiology, 2018-04-26) Guirao-Abad, José Pedro; Sánchez-Fresneda, Ruth; Machado, Francisco; Argüelles, Juan Carlos; Martínez-Esparza Alvargonzález, María Concepción; Bioquímica y Biología Molecular B e InmunologíaMicafungin belongs to the antifungal family of echinocandins, which act as noncompetitive inhibitors of the fungal cell wall β-1,3-d-glucan synthase. Since Candida albicans is the most prevalent pathogenic fungus in humans, we study the involvement of micafungin in the modulation of the inflammatory response developed by human tissue macrophages against C. albicans The MIC for micafungin was 0.016 μg/ml on the C. albicans SC5314 standard strain. Micafungin induced a drastic reduction in the number of exponential SC5314 viable cells, with the fungicidal effect being dependent on the cellular metabolic activity. Notably, micafungin also caused a structural remodelling of the cell wall, leading to exposure of the β-glucan and chitin content on the external surface. At the higher doses used (0.05 μg/ml), the antifungal also induced the blowing up of budding yeasts. In addition, preincubation with micafungin before exposure to human tissue macrophages enhanced the secretion of tumor necrosis factor alpha (TNF-α), interleukin-17A (IL-17A), and IL-10 cytokines. Our results strongly suggest that in C. albicans treatment with micafungin, in addition to having the expected toxic antifungal effect, it potentiates the immune response, improving the interaction and activation of human macrophages, probably through the unmasking of β-glucans on the cell wall surface.- PublicationOpen AccessMitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense(Nature, 2016) Garaude, Johan; Acín-Pérez, Rebeca; Martínez-Cano, Sarai; Enamorado, Michael; Ugolini, Matteo; Nistal-Villan, Estanislao; Hervás-Stubbs, Sandra; Pelegrin, Pablo; Sander, Leif E.; Enríquez, José A.; Sancho, David; Bioquímica y Biología Molecular B e InmunologíaThe mitochondrial electron transport chain (ETC) is a metabolic hub whose adaptations accompany fuel source fluctuations, stress responses, and innate immune signals to ensure optimal cellular functions. Macrophages tightly scale their core metabolism upon activation by innate immune receptors but the precise regulation of the ETC upon pathogen recognition and its functional implications are currently unknown. Here we show that innate immune sensing of live bacteria by macrophages elicits transient ETC adaptations that is characterized by a decrease assembly of complex I (CI) and CI-containing supercomplexes and by a switch in the relative contribution of complexes I and II to mitochondrial respiration. This is mediated by the phagosomal nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and the reactive oxygen species (ROS)-dependent Src-family tyrosine-kinase Fgr and required Toll-like receptor (TLR) signalling and the NOD-like receptor (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome, both connected to bacterial viability-specific immune responses. Consistently, the inhibition of CII in E. coli infected mice decreases IL-1b and increases IL-10 serum-levels to those found in mice treated with dead bacteria and impairs control of bacteria. We thus identify the innate immune receptor-mediated ETC adaptations as an early immune-metabolic checkpoint that potentially adjusts innate immune responses during bacterial infection.
- PublicationOpen AccessNeutrophils as a source of cytokines in inflammation(Murcia : F. Hernández, 1999) Matsukawa, A.; Yoshinaga, M.The recruitment of neutrophils into inflammatory foci is a fundamental process observed in inflammation. The function of neutrophils has long been regarded only as an effector cell that kills the invading pathogens. Recent evidence has demonstrated that neutrophils are capable of producing inflammatory cytokines. The findings are, however, mainly based on the findings obtained in vitro. It has not been fully elucidated if neutrophils could synthesize and secrete cytokines in vivo. Animal models of inflammation are essential to address the issue and provide insight into the involvement of neutrophils in producing cytokines.
- PublicationOpen AccessRole of cytokines in host defense against Staphylococcus aureus skin infection(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Wu, Guosheng; Zhu, Banghui; Hong, Xudong; Luo, Pengfei; Xia, ZhaofanWound infection caused by Staphylococcus aureus (S. aureus) is a critical clinical problem due to long hospitalization times, significant morbidity and mortality, as well as considerable medical resource consumption. With the emergence of methicillinresistant S. aureus (MRSA) strains, current antibiotic treatments are becoming ineffective in combatting S. aureus infection. Thus, a novel therapeutic strategy is required. Recent studies discovered that several cytokines in the infected wound area play protective roles against S. aureus infection. This review summarizes recent discoveries regarding the role of cytokines-mediated responses in host defense against S. aureus skin infection, and discusses their implications for future immunotherapy and vaccine development.
- PublicationOpen AccessTGF-ß1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1 ß(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Tsai, S. Y.; Schluns, K. S.; Le, P. T.; McNulty, J. A.T he pineal g land is part of th e neur oendoc rin e system that modulat es immun e functions. Beca use the gland is outside the blood-brain barrier, il is accessibl e to dir ec t feedback from circul atin g cyto kin es that affec t th e sy nth esis and secreti on of melatonin . Recent studi es have suggested that intrinsic immunoregul atory cytokines med iate these neuro-immune int e ra cti o ns und er th e co ntr o l of sympathetic innervation to the pineal. This study focused on th e expression of transfo rmin g growt h factor-f3 1 (TGF-f3I) and interl eukin-6 (IL-6), two cy toki nes th at have important regula tory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-f3l, but not IL-6, was expressed in freshly dissected rat pineal glands from neo natal age (l -day-o ld) into ad ults. Immun ocy toc hemistry for TGF-B1 in adult glands revealed localization of this protein in astrocy telik e cells. The sy mp ath e tic ne ur o tr ansmitt e r norepinephrine (NE) increased transcript levels for both TGF-f31 and IL-6 in adu lt pinea l organ cultures. The effect of NE o n I L-6 exp ressio n was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregul atory molecule interleukin-l/3 (IL-l /3) up-regulat ed th e expression of both IL-6 and TGF-/31 in ad ult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF- /31 and IL-6 have intrinsic regul atory roles in the pinea l gland and that both neural and immune factors are important mechanisms of regulation.
- PublicationOpen AccessThe effects of dexpanthenol in streptozotocin-induced diabetic rats: Histological, histochemical and immunological evidences(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Gulle, K.; Ceri, N.G.; Akpolat, M.; Arasli, M.; Demirci, B.This study was designed to investigate the effects of Dexpanthenol (Dxp) on liver and pancreas histology and cytokine levels in streptozotocine (STZ)- induced diabetic rats. Twenty-four Wistar albino male rats were divided into four groups: control, Dxp, STZinduced diabetic (STZ) and diabetic treatment with Dexpanthenol (STZ-Dxp) groups. Experimental diabetes was induced by single dose STZ (50 mg/kg) intraperitoneally (i.p.). After administration of STZ, the STZ-Dxp group began to receive a 300 mg/kg/day i.p. dose of Dxp for 6 weeks. Liver and pancreas tissues of the control group were in normal morphology. Liver tissue of STZ group showed vacuolisation of hepatocytes in the liver parenchyma with enlargement of sinusoidal spaces and increasing amounts of connective tissue in the portal area. Pancreatic section of STZ group displayed β-cells with of cytoplasmic mass, reduction of islet size, and atrophy. The STZ-Dxp group that received Dxp treatment exhibit partially normal hepatic parenchyma. Histochemical examinations revealed that the diabetes-induced glycogen depletion markedly improved with the Dxp treatment (p<0.001). The severity of degenerative alteration was lessened by Dxp supplementation in the STZ-Dxp group. Induction of STZ presented a significant increase both in interleukin1α (IL-1α) (p=0.033) and monocyte chemotactic protein-1 (MCP-1) (p=0.011) levels, when compared with the control rats. DXP-treated diabetic rats’ IL-1α and MCP-1 levels were similar to control value. This evidence suggests that Dxp is effective in reducing STZinduced, diabetic-related complications and may be beneficial for the treatment of diabetic patients.
- PublicationOpen AccessThe hepatic perisinusoidal stellate cell(Murcia : F. Hernández, 1997) Kawada, N.Hepatic stellate cell (also referred to as Ito cell, fat-storing cell, perisinusoidal cell, lipocyte) is one of the sinusoid-constituent cells that play multiple roles in liver pathophysiology. Although identification of the stellate cell had taken about 100 years because of the misconception caused by the discoverer von Kupffer, Wake made a great contribution to the "re"discovery of the cell in 1971. Establishment of the isolation of hepatic non-parenchymal cells from rats by Knook has made it possible to uncover the metabolic function of individual cells. Now, the stellate cell function is expanding from a retinol (fat)-storing site to a center of extracellular matrix metabolism and mediator production in the liver. Function as a liver specific pericyte has also been elucidated. Transition of the stellate cells from the vitamin A-storing phenotype to "activated" or "myofibroblastic" cells that produce a large amount of type 1 collagen and transfonning growth factor P triggers the progress of liver fibrosis in the course of hepatic inflamrnation. Comrnunication of the stellate cells with the other hepatic constituent cells and invading inflammatory cells is also an important factor that regulates the local pathological reaction. Analysis of cellular and molecular aspects of the stellate cell activation would lead to the establishment of a novel therapeutic strategy against the progress of liver fibrosis in human liver disease.
- PublicationOpen AccessThe tumor necrosis factor a of the bony fish seabream exhibits the in vivo proinflammatory and proliferative activities of its mammalian counterparts, yet it functions in a species-specific manner(Springer, 2004) García-Castillo, Jesús; Chaves-Pozo, Elena; Olivares, Pedro; Pelegrin, Pablo; Meseguer, José; Mulero Méndez, Victoriano Francisco; Bioquímica y Biología Molecular B e InmunologíaInformation on the bioactivities of non-mammalian cytokines is scant due to the lack of the recombinant molecules and specific antibodies. We produced the mature predicted peptide of tumor necrosis factor a (TNFa) from the bony fish gilthead seabream (Sparus aurata L.) (sbTNFa), and its biological role was determined in vitro and in vivo. We first demonstrated by analytical size-exclusion chromatography that sbTNFa is an oligomeric protein but the dimer appears to predominate over the trimeric form, in contrast to mammalian TNFa. Intraperitoneal injection of native sbTNFa resulted in (i) priming of the respiratory burst of the peritoneal exudate and head-kidney (HK) leukocytes, the latter being the bone marrow equivalent in fish; (ii) rapid recruitment of phagocytic granulocytes to the injection site, and (iii) induction of granulopoiesis in the HK. Interestingly, sbTNFa was able to induce a strong proliferation of HK cells in vitro, whereas human TNFa did not. Conversely, sbTNFa was not cytotoxic for murine L929 fibroblasts.
- PublicationOpen AccessTight junction proteins and signal transduction pathways in hepatocytes(Murcia : F. Hernández, 2009) Kojima, Takashi; Murata, Masaki; Yamamoto, Toshinobu; Lan, Mengdong; Imamura, Masafumi; Son, Seiichi; Takano, Ken-ichi; Yamaguchi, Hiroshi; Ito, Tatsuya; Tanaka, Satoshi; Chiba, Hideki; Hirata, Koichi; Sawada, NorimasaTight junctions of hepatocytes play crucial roles in the barrier to keep bile in bile canaliculi away from the blood circulation, which we call the bloodbilliary- barrier (Kojima et al., 2003). Tight junction proteins of hepatocytes are regulated by various cytokines and growth factors via distinct signal transduction pathways. They are also considered to participate in signal transduction pathways that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. This review focuses on recent findings about the relationship between tight junction proteins and signal transduction pathways in hepatocytes.