Browsing by Subject "CYTOKINE"

Sort by: Order: Results:

Now showing items 1-11 of 11
  • Savolainen, Laura E.; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara (2016)
    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-gamma, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-gamma, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette Guerin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative -stimulated IFN-gamma, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-gamma, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-gamma, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential.
  • Hasan, Amal; Kochumon, Shihab; Al-Ozairi, Ebaa; Tuomilehto, Jaakko; Al-Mulla, Fahd; Ahmad, Rasheed (2020)
    Purpose: The suppression of tumorigenicity 2 (ST2) has two main splice variants including a membrane bound (ST2) form, which activates the myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-kappa B) signaling pathway, and a secreted soluble form (sST2), which acts as a decoy receptor for ST2 ligand, interleukin (IL)-33. The IL-33/ST2 axis is protective against obesity, insulin resistance, and type 2 diabetes (T2D). In humans, adipose tissue IL-33 displays distinct correlation profiles with glycated hemoglobin, ST2, and other immunometabolic mediators, depending on the glycemic health of the individuals. We determined whether adipose tissue ST2 displays distinct correlation profiles with immunometabolic mediators and whether ST2 and/or IL-33 are correlated with intracellular signaling molecules. Patients and Methods: A total of 91 adults with normal glycemia, prediabetes, and T2D were included. After measuring their anthropometric and biochemical parameters, subcutaneous adipose tissues were isolated and mRNA expression of biomarkers was measured. Results: In individuals with normal glycemia, adipose tissue ST2 was directly correlated with chemokine (C-C motif) ligand (CCL)-2, CCL5, IL-12, fibrinogen-like protein 2 (FGL2) and interferon regulatory factor (IRF)-4, but inversely correlated with cytochrome C oxidase subunit 7A1. IL-33 and ST2 were directly correlated with tumor necrosis factor receptorassociated factor 6 (TRAF6), NF-kappa B, and nuclear factor of activated T-cells 5 (NFAT5). In individuals with prediabetes, ST2 was inversely correlated with IL-5, whereas IL-33 but not ST2 was directly correlated with MyD88 and NF-kappa B. In individuals with T2D, ST2 was directly correlated with CCL2, IL-1 beta, and IRF5. IL-33 and ST2 were directly correlated with MyD88, TRAF6, and NF-kappa B. Conclusion: Adipose tissue ST2 and IL-33 show different correlation profiles with various immunometabolic biomarkers depending on the metabolic state of the individuals. Therefore, targeting the IL-33/ST2 axis might form the basis for novel therapies to combat metabolic disorders.
  • Niemela, Tytti Maaria; Tulamo, Riitta-Mari; Uriel Carmona, Jorge; Lopez, Catalina (2019)
    Background: Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E-2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-beta(1) and TNF-alpha concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL). Results: Operation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-beta(1) and TNF-alpha concentrations but compared with baseline, synovial fluid IL-1ra and TNF-alpha concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen. Conclusions: Creation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-alpha concentrations but changes in concentrations of anabolic growth factors TGF-beta(1) and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.
  • Heikelä, Hanna; Ruohonen, Suvi T.; Adam, Marion; Viitanen, Riikka; Liljenback, Heidi; Eskola, Olli; Gabriel, Michael; Mairinoja, Laura; Pessia, Alberto; Velagapudi, Vidya; Roivainen, Anne; Zhang, Fu-Ping; Strauss, Leena; Poutanen, Matti (2020)
    Hydroxysteroid 17-beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within six days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males, 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity, specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Pro-inflammatory cytokines, such as interleukin 6 (IL-6), IL-17 and granulocyte-colony stimulating factor were increased in the HSD17B12cKO mice indicating inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in the fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis, and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
  • Nissinen, R.; Leirisalo-Repo, M; Nieminen, A. M.; Halme, L.; Färkkilä, M.; Palosuo, T.; Vaarala, O. (2004)
    Objectives: To determine whether inflammation in the gut associated immune system is activated in rheumatoid arthritis ( RA). The expression of chemokine receptor- (CCR4, CCR5) and cytokine- ( interleukin (IL) 2, IL10, interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha), and transforming growth factor beta (TGFbeta)) specific mRNA in intestinal biopsy samples from patients with RA was examined. Methods: Duodenal biopsy samples from 13 patients with RA and 15 control subjects were studied. The mRNA expression of CCR4, CCR5, IL2, IL10, IFNgamma, TNFalpha, and TGFb in intestinal biopsy samples was demonstrated by real time quantitative reverse transcriptase-polymerase chain reaction. Results: The mRNA expression of CCR4, CCR5, and IL10 in intestinal biopsy samples was increased in patients with RA in comparison with control subjects ( p = 0.001, p = 0.046, p = 0.019). No difference in the expression levels of IL2, IFNgamma, TNFalpha, or TGFbeta was seen between patients with RA and controls. Conclusions: The increased intestinal mRNA expression of IL10, CCR5, and CCR4 suggests that gut associated immune cells are activated in patients with RA.
  • Tatu, Alin Laurentiu; Nadasdy, Thomas; Arbune, Anca; Chioncel, Valentin; Bobeica, Carmen; Niculet, Elena; Iancu, Alina Viorica; Dumitru, Caterina; Popa, Valentin Tudor; Kluger, Nicolas; Clatici, Victor Gabriel; Vasile, Claudiu Ionut; Onisor, Cristian; Nechifor, Alexandru (2022)
    The interrelations and sequencing of interleukins are complex (inter)actions where each interleukin can stimulate the secretion of its preceding interleukin. In this paper, we attempt to summarize the currently known roles of IL-4, IL-13, IL-31, and IL -33 from a multi-disciplinary perspective. In order to conduct a comprehensive review of the current literature, a search was conducted using PubMed, Google Scholar, Medscape, UpToDate, and Key Elsevier for keywords. The results were compiled from case reports, case series, letters, and literature review papers, and analyzed by a panel of multi-disciplinary specialist physicians for relevance. Based on 173 results, we compiled the following review of interleukin signaling and its clinical significance across a multitude of medical specialties. Interleukins are at the bed rock of a multitude of pathologies across different organ systems and understanding their role will likely lead to novel treatments and better outcomes for our patients. New interleukins are being described, and the role of this inflammatory cascade is still coming to light. We hope this multi-discipline review on the role interleukins play in current pathology assists in this scope.
  • Kolosowska, Natalia; Gotkiewicz, Maria; Dhungana, Hiramani; Giudice, Luca; Giugno, Rosalba; Box, Daphne; Huuskonen, Mikko T.; Korhonen, Paula; Scoyni, Flavia; Kanninen, Katja M.; Yla-Herttuala, Seppo; Turunen, Tiia A.; Turunen, Mikko P.; Koistinaho, Jari; Malm, Tarja (2020)
    Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.
  • Waldenstrom, Jesper; Hellstrand, Kristoffer; Westin, Johan; Nilsson, Staffan; Christensen, Peer; Färkkilä, Martti; Morch, Kristine; Langeland, Nina; Norkrans, Gunnar; Lagging, Martin (2021)
    Objectives: Despite recombinant interferon-lambda 4 (IFN-lambda 4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that IFN-?A may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV). Materials and methods: Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay. Results: Patients producing IFN-lambda 4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-lambda 4 (IFNL4(rs1)(2979860) CT/TT versus CC, p Conclusions: To our knowledge, this is the first report that demonstrates that the ability to produce IFN-lambda 4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-lambda 4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection.
  • Munsterhjelm, Camilla Marianne; Nordgreen, Janicke; Aae, F.; Heinonen, Mari Leena; Valros, Anna Elisabet; Janczak, A. M. (2019)
    Poor health is associated with an increased risk of tail biting outbreaks in pigs. We propose that this is because illness changes social dynamics either by changing the behaviour of the sick pig towards its penmates, the behaviour of the healthy penmates towards the sick pig, or both. We tested the effect of immune stimulation (lipopolysaccharide (LPS) injection: O111:B4; 1.5 mu g kg(-1) IV) on social behaviour in gilts housed in triplets in a cross-over experiment. Each pen was subjected to the control treatment (all three pigs injected with saline) and then LPS treatment (one pig injected with LPS, two injected with saline), or vice versa. LPS injected pigs had a shift in social motivation and performed more tail- and ear- directed behaviour than saline pigs two days after injection. They seemed to fit the description of 'sick and grumpy'. This change was seen about 40 h after the signs of acute illness dissipated and was not accompanied by a similar increase in activity. We discuss possible mechanisms for this behavioural change in light of changes in neurotransmitter levels at three days after LPS injection described in a previous experiment.
  • Korhonen, Eveliina; Bisevac, Jovana; Hyttinen, Juha M. T.; Piippo, Niina; Hytti, Maria; Kaarniranta, Kai; Petrovski, Goran; Kauppinen, Anu (2020)
    PURPOSE. The cornea is continually exposed to highly energetic solar UV-B (280-320 nm). Our aim was to investigate whether UV-B triggers the activation of NLRP3 inflammasomes and the production of IL-1 beta and/or IL-18 in human corneal epithelial (HCE) cells. Additionally, we studied the capability of cis-urocanic acid (cis-UCA) to prevent inflammasome activation or alleviate inflammation through other signaling pathways. METHODS. HCE-2 cell line and primary HCE cells were primed using lipopolysaccharide or TNF-alpha. Thereafter, cells were exposed to UV-B before or after the addition of cis-UCA or caspase-1 inhibitor. Caspase-1 activity was measured from cell lysates by an enzymatic assay. IL-1 beta, IL-18, IL-6, IL-8, and NLRP3 levels were detected using the ELISA method from cell culture media. Additionally, intracellular NLRP3 levels were determined by the Western blot technique, and cytotoxicity was measured by the LDH assay. RESULTS. UV-B exposure significantly increased caspase-1 activity in TNF-alpha-primed HCE cells. This result was consistent with the concurrently induced IL-1 beta secretion. Both caspase-1 activity and release of IL-1 beta were reduced by cis-UCA. Additionally, UV-B stimulated the caspase-1-independent production of IL-18, an effect also reduced by cis-UCA. Cis-UCA decreased the release of IL-6, IL-8, and LDH in a time-dependent manner when administered to HCE-2 cells after UV-B exposure. CONCLUSIONS. Our findings demonstrate that UV-B activates inflammasomes in HCE cells. Cis-UCA can prevent the secretion of IL-1 beta and IL-18 and therapeutically reduces the levels of IL-6, IL-8, and LDH in UV-B-stressed HCE cells.
  • Nordgaard, Cathrine; Vind, Anna Constance; Stonadge, Amy; Kjobsted, Rasmus; Snieckute, Goda; Antas, Pedro; Blasius, Melanie; Reinert, Marie Sofie; Del Val, Ana Martinez; Bekker-Jensen, Dorte Breinholdt; Haahr, Peter; Miroshnikova, Yekaterina A.; Mazouzi, Abdelghani; Falk, Sarah; Perrier-Groult, Emeline; Tiedje, Christopher; Li, Xiang; Jakobsen, Jens Rithamer; Jorgensen, Nicolas Oldenburg; Wojtaszewski, Jorgen F. P.; Mallein-Gerin, Frederic; Andersen, Jesper Lovind; Pennisi, Cristian Pablo; Clemmensen, Christoffer; Kassem, Moustapha; Jafari, Abbas; Brummelkamp, Thijn; Li, Vivian S. W.; Wickström, Sara A.; Olsen, Jesper Velgaard; Blanco, Gonzalo; Bekker-Jensen, Simon (2022)
    Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAK beta is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKO's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.