Pro-inflammatory cytokines and growth factors in human milk: an exploratory analysis of racial differences to inform breast cancer etiology.
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SUBMITTER: Murphy J
PROVIDER: S-EPMC6191357 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Project description:IntroductionNeuroinflammation has been established to be part of the neuropathological changes in Parkinson's disease (PD) and atypical parkinsonism (APD). Activated microglia play a key role in neuroinflammation by release of cytokines. Evidence of the disparity, if any, in the neuroinflammatory response between PD and APD is sparse. In this study, we investigated CSF cytokine profiles in patients with PD, multiple system atrophy (MSA), or progressive supranuclear palsy (PSP).MethodsOn a sensitive electrochemiluminescence-based platform (Quickplex, Meso Scale Discovery®), we examined a panel of C-reactive protein (CRP) and eight selected cytokines, IFN-?, IL-10, IL-18, IL-1?, IL-4, IL-6, TGF-?1, and TNF-?, among patients with PD (n?=?46), MSA (n?=?35), and PSP (n?=?39) or controls (n?=?31). Additionally, CSF total tau protein levels were measured as a marker of nonspecific neurodegeneration for correlation estimates.ResultsCRP and the pro-inflammatory cytokines TNF-?, IL-1?, and Il-6 were statistically significantly elevated in MSA and PSP patients compared to PD patients but not compared to control patients. No analytes differed statistically significantly between MSA and PSP patients. The best diagnostic discrimination, evaluated by ROC curve (AUC 0.77, p?=?007, 95% CI 0.660-0.867), between PD and MSA patients was seen for a subset of analytes: CRP, TNF-?, IL-1?, and IFN-?.ConclusionAmong the investigated cytokines and CRP, we found a statistically significant increase of microglia-derived cytokines in MSA and PSP patients compared to PD patients.
| S-EPMC6215346 | biostudies-literature
Project description:BackgroundCancer cachexia (CC) is a multifactorial syndrome, often irreversible, that affects patients with cancer influenced, in part, by the inflammatory condition. Peritumoural adipose tissue produces adipokines and angiogenic, apoptotic, and growth factors; given the possible crosstalk between the peritumoural adipose tissue and tumour, these may play an important role in cancer biology and carcinogenesis.MethodsThe aim of this study was to evaluate the factors produced by peritumoural adipose tissue in a cohort of 16 colorectal cancer patients with either weight-stable cancer (WSC; n = 7) or CC (n = 9). The study was approved by the Ethics Research Committee (972.914). Samples of peritumoural adipose tissue were analysed for concentrations of TNF-?, IL-1?, STAT-1, STAT-3, RANTES, IL-1Ra, IP-10, IL-15, MCP-1, IFN-?, GCSF, FADD, and TGF-?. The cytokines and proteins were measured using Multiplex. Correlations between the proteins and cytokines were evaluated.ResultsTNF-?, STAT-1, and FADD, a factor involved in apoptosis, were significantly higher in CC group than in the WSC group. In the peritumoural adipose tissue of the CC group, RANTES showed a significant positive correlation with IL-1Ra and IP-10 and a negative correlation with IFN-?; and GCSF showed significant negative correlations with IL-1Ra, IP-10, IL-15, and MCP-1 and a positive correlation with IFN-?. In the peritumoural adipose tissue of the WSC group, no significant correlations were detected between RANTES, GCSF, IL-3, FADD, and STAT-1 and the cytokines/chemokines analysed.ConclusionsThese results indicated that inflammatory and tumorigenic pathways were altered in peritumoural adipose tissue in CC. Furthermore, inflammatory cytokines were correlated with growth factors in the peritumoural adipose tissue of cachectic patients, suggesting that inflammatory cytokines modulated the proliferative environment closely linked to the tumour.
| S-EPMC6240753 | biostudies-literature
Project description:The well-recognized cell phenotypic heterogeneity in tumors is a great challenge for cancer treatment. Dynamic interconversion and movement within a spectrum of different cell phenotypes (cellular plasticity) with the acquisition of specific cell functions is a fascinating biological puzzle, that represent an additional difficulty for cancer treatment and novel therapies development. The understanding of the molecular mechanisms responsible for moving or stabilizing tumor cells within this spectrum of variable states constitutes a valuable tool to overcome these challenges. In particular, cell transitions between epithelial and mesenchymal phenotypes (EMT-MET) and de-and trans-differentiation processes are relevant, since it has been shown that they confer invasiveness, drug resistance, and metastatic ability, due to the simultaneous acquisition of stem-like cell properties. Multiple drivers participate in these cell conversions events. In particular, cellular senescence and senescence-associated soluble factors have been shown to unveil stem-like cell properties and cell plasticity. By modulating gradually the composition of their secretome and the time of exposure, senescent cells may have differential effect not only on tumor cells but also on surrounding cells. Intriguingly, tumor cells that scape from senescence acquire stem-like cell properties and aggressiveness. The reinforcement of senescence and inflammation by soluble factors and the participation of immune cells may provide a dynamic milieu having varied effects on cell transitions, reprogramming, plasticity, stemness and therefore heterogeneity. This will confer different epithelial/mesenchymal traits (hybrid phenotype) and stem-like cell properties, combinations of which, in a particular cell context, could be responsible for different cellular functions during cancer progression (survival, migration, invasion, colonization or proliferation). Additionally, cooperative behavior between cell subpopulations with different phenotypes/stemness functions could also modulate their cellular plasticity. Here, we will discuss the role of senescence and senescence-associated pro-inflammatory cytokines on the induction of cellular plasticity, their effect role in establishing particular states within this spectrum of cell phenotypes and how this is accompanied by stem-like cell properties that, as the epithelial transitions, may also have a continuum of characteristics providing tumor cells with functional adaptability specifically useful in the different stages of carcinogenesis.
| S-EPMC7237636 | biostudies-literature
Project description:IntroductionThe pro- and anti-inflammatory cytokines play crucial role in the development and functions of placenta. Any changes in these cytokines may be associated with many pregnancy-related disorders like preeclampsia. Therefore, the present study is aimed to study the expression of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in placenta and serum of preeclamptic pregnant women.Material and methodsFor this study, a total of 194 cases of preeclamptic and control cases were enrolled in two Groups as per the gestational age that is, Group I (28-36 weeks) and II (37 weeks onwards). The number of samples was 55 in Group I and 139 in Group II. The immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were conducted on placenta and serum of both preeclamptic and normal samples, respectively. IHC results were revalidated by reverse transcriptase PCR (RT-PCR).ResultsBoth Groups (I, II) of preeclampsia showed amended levels of pro- and anti-inflammatory cytokines in placental tissues and serum samples. The levels of TNF-α and IL-6 were significantly increased in preeclamptic cases (P = 0.0001, P = 0.0001) while the IL-4 and IL-10 were downregulated (P = 0.0001, P = 0.0001) in comparison to control. In addition, a negative correlation was also observed between the two in preeclampsia (P = 0.0001).ConclusionThe balanced ratio of pro- and anti-inflammatory cytokines is essential to regulate the maternal inflammation system throughout pregnancy. Therefore, the gradual cytokine profiling of the pregnant women may be useful for the management of preeclampsia.
| S-EPMC6528584 | biostudies-literature
Project description:Mutations in Lamin A/C gene (lmna) cause a wide spectrum of cardiolaminopathies strictly associated with significant deterioration of the electrical and contractile function of the heart. Despite the continuous flow of biomedical evidence, linking cardiac inflammation to heart remodelling in patients harbouring lmna mutations is puzzling. Therefore, we profiled 30 serum cytokines/chemokines in patients belonging to four different families carrying pathogenic lmna mutations segregating with cardiac phenotypes at different stages of severity (n = 19) and in healthy subjects (n = 11). Regardless lmna mutation subtype, high levels of circulating granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) were found in all affected patients' sera. In addition, elevated levels of Interleukins (IL) IL-1Ra, IL-1β IL-4, IL-5 and IL-8 and the granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in a large subset of patients associated with more aggressive clinical manifestations. Finally, the expression of the pro-inflammatory 70 kDa heat shock protein (Hsp70) was significantly increased in serum exosomes of patients harbouring the lmna mutation associated with the more severe phenotype. Overall, the identification of patient subsets with overactive or dysregulated myocardial inflammatory responses could represent an innovative diagnostic, prognostic and therapeutic tool against Lamin A/C cardiomyopathies.
| S-EPMC8642682 | biostudies-literature
Project description:Comparison of libraries derived from primary human bronchial epithelial cells which are [i] unstimulated, [ii] stimulated with the pro-inflammatory cytokines IL1beta and TNFalpha and [iii] stimulated with heat-inactivated Pseudomonas aeruginosa (strain PAO1). Keywords: other
2005-02-02 | E-GEOD-2056 | biostudies-arrayexpress
Project description:The present study was undertaken to evaluate serum levels of pro-inflammatory cytokines in Tunisian older adults and to examine the relationships between inflammatory marker levels, geriatric, and biochemical parameters. A cross-sectional study was conducted in a population of Tunisian older adults (N = 141, aged 65 and over). Patients were recruited from the Department of Internal Medicine, Fattouma Bourguiba University Hospital (Monastir, Tunisia) and from a nursing home (Sousse, Tunisia). Comprehensive geriatric assessment, history taking and examination including functional and nutritional assessment were done for each participant. Enzyme-linked immunosorbent assay (ELISA) test was used to measure serum cytokine (TNF-α, IL-8, IL-6) levels. The modified Short Emergency Geriatric Assessment score (SEGAm) were used to classify patients as 51 very-frail, 40 frail, and 50 non-frail. The age of the participants (80 men, 61 women) ranged from 65 to 97 years. Serum levels of TNF-α, IL-8 and C-reactive protein (CRP) were significantly higher in very-frail participants compared to frail and non-frail ones. However, no significant differences in IL-6 levels were detected among frailty groups. After adjustment for age, CRP and IL-8 levels remained significantly associated with frailty. Analysis of the receiver operating characteristic (ROC) curve corresponding to IL-8 showed an area under the curve of 0.7 (p = 0.003; 95% CI [0.58-0.81]) and a predictive threshold of 5.27 pg/ml. Positive correlations were found between frailty score, IL-6, and IL-8 levels. In addition, a significant positive correlation was observed between IL-8 levels and Timed Up and Go test results. However, a negative correlation was observed between Mini Nutritional Assessment Short-Form score, IL-6 and CRP levels, as well as between Activities of Daily Living score and serum levels of TNF-α, IL-6, and CRP. In conclusion, the key findings of this study collectively support a role of pro-inflammatory cytokines, TNF-α, CRP, and especially IL-8 in the development of frailty in older adults.
| S-EPMC7652286 | biostudies-literature
Project description:We have used RNA-seq to identify transcripts, including splice variants, expressed in human islets of Langerhans under control condition or following exposure to the pro-inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets. 25/41 of the candidate genes for type 1 diabetes are expressed in islets, and cytokines modified expression of several of these transcripts. 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)
2012-03-09 | E-GEOD-35296 | biostudies-arrayexpress
Project description:Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term 'cytokine storm syndrome' is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.
| S-EPMC7536084 | biostudies-literature
Project description:BACKGROUND:Chondrocytes are exposed to an inflammatory micro-environment in the extracellular matrix (ECM) of articular cartilage in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA, degenerative changes and low-grade inflammation within the joint transform the behaviour and metabolism of chondrocytes, disturb the balance between ECM synthesis and degradation, and alter the osmolality and ionic composition of the micro-environment. We hypothesize that chondrocytes adjust their physiology to the inflammatory microenvironment by modulating the expression of cell surface proteins, collectively referred to as the 'surfaceome'. Therefore, the aim of this study was to characterize the surfaceome of primary equine chondrocytes isolated from healthy joints following exposure to the pro-inflammatory cytokines interleukin-1-beta (IL-1?) and tumour necrosis factor-alpha (TNF-?). We employed combined methodology that we recently developed for investigating the surfaceome in stem cells. Membrane proteins were isolated using an aminooxy-biotinylation technique and analysed by mass spectrometry using high throughput shotgun proteomics. Selected proteins were validated by western blotting. RESULTS:Amongst the 431 unique cell surface proteins identified, a high percentage of low-abundance proteins, such as ion channels, receptors and transporter molecules were detected. Data are available via ProteomeXchange with identifier PXD014773. A high number of proteins exhibited different expression patterns following chondrocyte stimulation with pro-inflammatory cytokines. Low density lipoprotein related protein 1 (LPR-1), thrombospondin-1 (TSP-1), voltage dependent anion channel (VDAC) 1-2 and annexin A1 were considered to be of special interest and were analysed further by western blotting. CONCLUSIONS:Our results provide, for the first time, a repository for proteomic data on differentially expressed low-abundance membrane proteins on the surface of chondrocytes in response to pro-inflammatory stimuli.
| S-EPMC7318434 | biostudies-literature