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7. The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.

Author

Koivisto, Katri, Karppinen, Jaro, Haapea, Marianne, Järvinen, Jyri, Kyllönen, Eero, Tervonen, Osmo, Niinimäki, Jaakko, Alini, Mauro, Lotz, Jeffrey, Dudli, Stefan, Samartzis, Dino, Risteli, Juha, Majuri, Marja-Leena, Alenius, Harri, and Grad, Sibylle

Subjects
Modic change, chronic low back pain, magnetic resonance imaging, randomized trial, serum biomarkers, zoledronic acid
Abstract

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini-Hochberg (B-H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

Published
2019

8. Influence of FLG loss-of-function mutations in host–microbe interactions during atopic skin inflammation

Author

Oláh, Peter, Szlávicz, Eszter, Kuchner, Marcus, Nemmer, Jana, Zeeuwen, Patrick, Lefèvre-Utile, Alain, Fyhrquist, Nanna, Prast-Nielsen, Stefanie, Skoog, Tiina, Serra, Angela, Rodríguez, Elke, Raap, Ulrike, Meller, Stephan, Gyulai, Rolland, Hupé, Philippe, Kere, Juha, Levi-Schaffer, Francesca, Tsoka, Sophia, Alexander, Helen, Nestle, Frank O., Schröder, Jens M., Weidinger, Stephan, van den Bogaard, Ellen, Soumelis, Vassili, Greco, Dario, Barker, Jonathan, Lauerma, Antti, Ranki, Annamari, Andersson, Björn, Alenius, Harri, and Homey, Bernhard

Published
2022
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9. Biomarkers of nanomaterials hazard from multi-layer data

Author

Fortino, Vittorio, Kinaret, Pia Anneli Sofia, Fratello, Michele, Serra, Angela, Saarimäki, Laura Aliisa, Gallud, Audrey, Gupta, Govind, Vales, Gerard, Correia, Manuel, Rasool, Omid, Ytterberg, Jimmy, Monopoli, Marco, Skoog, Tiina, Ritchie, Peter, Moya, Sergio, Vázquez-Campos, Socorro, Handy, Richard, Grafström, Roland, Tran, Lang, Zubarev, Roman, Lahesmaa, Riitta, Dawson, Kenneth, Loeschner, Katrin, Larsen, Erik Husfeldt, Krombach, Fritz, Norppa, Hannu, Kere, Juha, Savolainen, Kai, Alenius, Harri, Fadeel, Bengt, and Greco, Dario

Published
2022
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10. A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes.

Author

del Giudice, Giusy, Serra, Angela, Pavel, Alisa, Torres Maia, Marcella, Saarimäki, Laura Aliisa, Fratello, Michele, Federico, Antonio, Alenius, Harri, Fadeel, Bengt, and Greco, Dario

Subjects
TOXICOLOGY, BIOLOGICAL systems, LIFE sciences, NANOSTRUCTURED materials, SYSTEMS theory, SYSTEMS biology
Abstract

Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network‐based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network‐based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data‐driven approaches for the hazard assessment of nanomaterials and other advanced materials. [ABSTRACT FROM AUTHOR]

Published
2024
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15. ZnO Nanoparticles as Potent Inducers of Dermal Immunosuppression in Contact Hypersensitivity in Mice

Author

Wang, Shuyuan, Ilves, Marit, Mäenpää, Kuunsäde, Zhao, Lan, El-Nezami, Hani, Karisola, Piia, and Alenius, Harri

Abstract

Nanosized zinc oxide (nZnO) metal particles are used in skin creams and sunscreens to enhance their texture and optical properties as UV filters. Despite their common use, little is known about the molecular mechanisms of nZnO exposure on damaged skin. We studied the effects of topically applied nZnO particles on allergic skin inflammation in an oxazolone (OXA)-induced contact hypersensitivity (CHS) mouse model. We investigated whether exposure to nZnO during the sensitization or challenge phase would induce immunological changes and modulate transcriptional responses. We followed skin thickness, cellular infiltration, and changes in the local transcriptome up to 28 days after the challenge. The responses peaked at 24 h and were fully resolved by 28 days. Co-exposure to nZnO and hapten did not interfere with the formation of the sensitization process. Conversely, during the hapten challenge, the application of nZnO fully suppressed the development of the CHS response by the inhibition of pro-inflammatory pathways, secretion of pro-inflammatory cytokines, and proliferation of immune cells. In differentiated and stimulated THP-1 cells and the CHS mouse model, we found that nZnO particles and Zn ions contributed to anti-inflammatory responses. The immunosuppressive properties of nZnO in inflamed skin are mediated by impaired IL-1R-, CXCR2-, and LTB4-mediated pathways. nZnO-induced dermal immunosuppression may be beneficial for individuals with contact allergies who use nZnO-containing cosmetic products. Our findings also provide a deeper understanding of the mechanisms of nZnO, which could be considered when developing nanoparticle-containing skin products.

Published
2024
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19. Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor

Author

Karolinska Institute, European Commission, Peng, Guotao [0000-0001-7169-9961], Alenius, Harri [0000-0003-0106-8923], Lozano, Neus [0000-0002-9026-1743], Kostarelos, Kostas [0000-0002-2224-6672], Fadeel, Bengt [0000-0001-5559-8482], Peng, Guotao, Sinkko, Hanna M., Alenius, Harri, Lozano, Neus, Kostarelos, Kostas, Bräutigam, Lars, Fadeel, Bengt, Karolinska Institute, European Commission, Peng, Guotao [0000-0001-7169-9961], Alenius, Harri [0000-0003-0106-8923], Lozano, Neus [0000-0002-9026-1743], Kostarelos, Kostas [0000-0002-2224-6672], Fadeel, Bengt [0000-0001-5559-8482], Peng, Guotao, Sinkko, Hanna M., Alenius, Harri, Lozano, Neus, Kostarelos, Kostas, Bräutigam, Lars, and Fadeel, Bengt

Abstract

The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in the gut1,2. Here we show that oral exposure to graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish, with significant differences in wild-type versus ahr2-deficient animals. Furthermore, GO was found to elicit AhR-dependent induction of cyp1a and homing of lck+ cells to the gut in germ-free zebrafish larvae when combined with the short-chain fatty acid butyrate. To obtain further insights into the immune responses to GO, we used single-cell RNA sequencing to profile cells from whole germ-free embryos as well as cells enriched for lck. These studies provided evidence for the existence of innate lymphoid cell (ILC)-like cells3 in germ-free zebrafish. Moreover, GO endowed with a 'corona' of microbial butyrate triggered the induction of ILC2-like cells with attributes of regulatory cells. Taken together, this study shows that a nanomaterial can influence the crosstalk between the microbiome and immune system in an AhR-dependent manner.

Published
2023

22. A sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: Involvement of TRPV1 and TRPA1

Author

Cevikbas, Ferda, Wang, Xidao, Akiyama, Tasuku, Kempkes, Cordula, Savinko, Terhi, Antal, Attila, Kukova, Gabriela, Buhl, Timo, Ikoma, Akihiko, Buddenkotte, Joerg, Soumelis, Vassili, Feld, Micha, Alenius, Harri, Dillon, Stacey R, Carstens, Earl, Homey, Bernhard, Basbaum, Allan, and Steinhoff, Martin

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Immunology, Aetiology, 2.1 Biological and endogenous factors, Neurological, Inflammatory and immune system, Animals, Calcium Channels, Cells, Cultured, Female, Ganglia, Spinal, Humans, Interleukins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, Pruritus, Receptors, Interleukin, Sensory Receptor Cells, Skin, TRPA1 Cation Channel, TRPV Cation Channels, Th2 Cells, Transient Receptor Potential Channels, Cytokine, atopic dermatitis, sensory nerve, skin, transient receptor potential channel, AD, AITC, Allyl isothiocyanate, Atopic dermatitis, DRG, Dorsal root ganglia, ERK, Extracellular signal-regulated kinase, GRPR, Gastrin-releasing peptide receptor, HBSS, Hanks balanced salt solution, High-power field, IB4, Isolectin B4, KO, Knockout, MEK, Mas-related G protein–coupled receptor, Mitogen-activated protein kinase enzyme, Mrgpr, NPR-A, Natriuretic peptide receptor A, OSMRβ, OVA, Oncostatin M receptor β, Ovalbumin, PAR-2, Proteinase-activated receptor 2, Quantitative real-time PCR, SC, SEB, Spinal cord, Staphylococcal enterotoxin B, TG, TRPA1, TRPV1, Transient receptor channel potential cation channel ankyrin subtype 1, Transient receptor potential cation channel vanilloid subtype 1, Trigeminal ganglion, hpf, qPCR, Allergy
Abstract

BackgroundAlthough the cytokine IL-31 has been implicated in inflammatory and lymphoma-associated itch, the cellular basis for its pruritic action is yet unclear.ObjectiveWe sought to determine whether immune cell-derived IL-31 directly stimulates sensory neurons and to identify the molecular basis of IL-31-induced itch.MethodsWe used immunohistochemistry and quantitative real-time PCR to determine IL-31 expression levels in mice and human subjects. Immunohistochemistry, immunofluorescence, quantitative real-time PCR, in vivo pharmacology, Western blotting, single-cell calcium imaging, and electrophysiology were used to examine the distribution, functionality, and cellular basis of the neuronal IL-31 receptor α in mice and human subjects.ResultsAmong all immune and resident skin cells examined, IL-31 was predominantly produced by TH2 and, to a significantly lesser extent, mature dendritic cells. Cutaneous and intrathecal injections of IL-31 evoked intense itch, and its concentrations increased significantly in murine atopy-like dermatitis skin. Both human and mouse dorsal root ganglia neurons express IL-31RA, largely in neurons that coexpress transient receptor potential cation channel vanilloid subtype 1 (TRPV1). IL-31-induced itch was significantly reduced in TRPV1-deficient and transient receptor channel potential cation channel ankyrin subtype 1 (TRPA1)-deficient mice but not in c-kit or proteinase-activated receptor 2 mice. In cultured primary sensory neurons IL-31 triggered Ca(2+) release and extracellular signal-regulated kinase 1/2 phosphorylation, inhibition of which blocked IL-31 signaling in vitro and reduced IL-31-induced scratching in vivo.ConclusionIL-31RA is a functional receptor expressed by a small subpopulation of IL-31RA(+)/TRPV1(+)/TRPA1(+) neurons and is a critical neuroimmune link between TH2 cells and sensory nerves for the generation of T cell-mediated itch. Thus targeting neuronal IL-31RA might be effective in the management of TH2-mediated itch, including atopic dermatitis and cutaneous T-cell lymphoma.

Published
2014

26. DNA methylation in childhood asthma: an epigenome-wide meta-analysis

Author

Xu, Cheng-Jian, Söderhäll, Cilla, Bustamante, Mariona, Baïz, Nour, Gruzieva, Olena, Gehring, Ulrike, Mason, Dan, Chatzi, Leda, Basterrechea, Mikel, Llop, Sabrina, Torrent, Maties, Forastiere, Francesco, Fantini, Maria Pia, Carlsen, Karin C Lødrup, Haahtela, Tari, Morin, Andréanne, Kerkhof, Marjan, Merid, Simon Kebede, van Rijkom, Bianca, Jankipersadsing, Soesma A, Bonder, Marc Jan, Ballereau, Stephane, Vermeulen, Cornelis J, Aguirre-Gamboa, Raul, de Jongste, Johan C, Smit, Henriette A, Kumar, Ashish, Pershagen, Göran, Guerra, Stefano, Garcia-Aymerich, Judith, Greco, Dario, Reinius, Lovisa, McEachan, Rosemary R C, Azad, Raf, Hovland, Vegard, Mowinckel, Petter, Alenius, Harri, Fyhrquist, Nanna, Lemonnier, Nathanaël, Pellet, Johann, Auffray, Charles, van der Vlies, Pieter, van Diemen, Cleo C, Li, Yang, Wijmenga, Cisca, Netea, Mihai G, Moffatt, Miriam F, Cookson, William O C M, Anto, Josep M, Bousquet, Jean, Laatikainen, Tiina, Laprise, Catherine, Carlsen, Kai-Håkon, Gori, Davide, Porta, Daniela, Iñiguez, Carmen, Bilbao, Jose Ramon, Kogevinas, Manolis, Wright, John, Brunekreef, Bert, Kere, Juha, Nawijn, Martijn C, Annesi-Maesano, Isabella, Sunyer, Jordi, Melén, Erik, and Koppelman, Gerard H

Published
2018
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27. Characterization of a Common Susceptibility Locus for Asthma-Related Traits

Author

Laitinen, Tarja, Polvi, Anne, Rydman, Pia, Vendelin, Johanna, Pulkkinen, Ville, Salmikangas, Paula, Mäkelä, Siru, Rehn, Marko, Pirskanen, Asta, Rautanen, Anna, Zucchelli, Marco, Gullstén, Harriet, Leino, Marina, Alenius, Harri, Petäys, Tuula, Haahtela, Tari, Laitinen, Annika, Laprise, Catherine, Hudson, Thomas J., Laitinen, Lauri A., and Kere, Juha

Published
2004

28. Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women

Author

Alenius, Harri, Avendano, Mauricio, Barros, Henrique, Bochud, Murielle, Carmeli, Cristian, Carra, Luca, Castagné, Raphaele, Chadeau-Hyam, Marc, Clavel-Chapelon, Françoise, Costa, Giuseppe, Courtin, Emilie, Delpierre, Cyrille, D'Errico, Angelo, Dugué, Pierre-Antoine, Elliott, Paul, Fraga, Silvia, Gares, Valérie, Giles, Graham, Goldberg, Marcel, Greco, Dario, Hodge, Allison, Irving, Michelle Kelly, Karisola, Piia, Kivimäki, Mika, Krogh, Vittorio, Lang, Thierry, Layte, Richard, Lepage, Benoit, Mackenbach, Johan, Marmot, Michael, McCrory, Cathal, Milne, Roger, Muennig, Peter, Nusselder, Wilma, Panico, Salvatore, Petrovic, Dusan, Polidoro, Silvia, Preisig, Martin, Raitakari, Olli, Ribeiro, Ana Isabel, Ricceri, Fulvio, Robinson, Oliver, Valverde, Jose Rubio, Sacerdote, Carlotta, Satolli, Roberto, Severi, Gianluca, Shipley, Martin J, Stringhini, Silvia, Tumino, Rosario, Vineis, Paolo, Vollenweider, Peter, Zins, Marie, Jokela, Markus, Avendaño, Mauricio, Guida, Florence, d'Errico, Angelo, Giles, Graham G, Kelly-Irving, Michelle, Lasserre, Aurélie M, Marmot, Michael G, Kawachi, Ichiro, Steptoe, Andrew, and Mackenbach, Johan P

Published
2017
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29. Artificially cloaked viral nanovaccine for cancer immunotherapy

Author

Fusciello, Manlio, Fontana, Flavia, Tähtinen, Siri, Capasso, Cristian, Feola, Sara, Martins, Beatriz, Chiaro, Jacopo, Peltonen, Karita, Ylösmäki, Leena, Ylösmäki, Erkko, Hamdan, Firas, Kari, Otto K., Ndika, Joseph, Alenius, Harri, Urtti, Arto, Hirvonen, Jouni T., Santos, Hélder A., and Cerullo, Vincenzo

Published
2019
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30. Microbe-host interplay in atopic dermatitis and psoriasis

Author

Fyhrquist, Nanna, Muirhead, Gareth, Prast-Nielsen, Stefanie, Jeanmougin, Marine, Olah, Peter, Skoog, Tiina, Jules-Clement, Gerome, Feld, Micha, Barrientos-Somarribas, Mauricio, Sinkko, Hanna, van den Bogaard, Ellen H., Zeeuwen, Patrick L.J.M., Rikken, Gijs, Schalkwijk, Joost, Niehues, Hanna, Däubener, Walter, Eller, Silvia Kathrin, Alexander, Helen, Pennino, Davide, Suomela, Sari, Tessas, Ioannis, Lybeck, Emilia, Baran, Anna M., Darban, Hamid, Gangwar, Roopesh Singh, Gerstel, Ulrich, Jahn, Katharina, Karisola, Piia, Yan, Lee, Hansmann, Britta, Katayama, Shintaro, Meller, Stephan, Bylesjö, Max, Hupé, Philippe, Levi-Schaffer, Francesca, Greco, Dario, Ranki, Annamari, Schröder, Jens M., Barker, Jonathan, Kere, Juha, Tsoka, Sophia, Lauerma, Antti, Soumelis, Vassili, Nestle, Frank O., Homey, Bernhard, Andersson, Björn, and Alenius, Harri

Published
2019
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33. A short history from Karelia study to biodiversity and public health interventions

Author

Haahtela, Tari, primary, Alenius, Harri, additional, Auvinen, Petri, additional, Fyhrquist, Nanna, additional, von Hertzen, Leena, additional, Jousilahti, Pekka, additional, Karisola, Piia, additional, Laatikainen, Tiina, additional, Lehtimäki, Jenni, additional, Paalanen, Laura, additional, Ruokolainen, Lasse, additional, Saarinen, Kimmo, additional, Valovirta, Erkka, additional, Vasankari, Tuula, additional, Vlasoff, Tiina, additional, Erhola, Marina, additional, Bousquet, Jean, additional, Vartiainen, Erkki, additional, and Mäkelä, Mika J., additional

Published
2023
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41. Oral exposure to Ag or TiO2 nanoparticles perturbed gut transcriptome and microbiota in a mouse model of ulcerative colitis : Ag or TiO2 nanoparticles in ulcerative colitis

Author

Wang, Shuyuan, Kang, Xing, Alenius, Harri, Wong, Sunny Hei, Karisola, Piia, El-Nezami, Hani, Doctoral school in biological, environmental and food sciences, HUMI - Human Microbiome Research, Doctoral Programme in Microbiology and Biotechnology, Biosciences, and Doctoral Programme in Integrative Life Science

Subjects
16S sequencing, Inflammation, Nanoparticles, Metal oxides, Gut microbiota, 3111 Biomedicine, DSS-Induced colitis, RSEQ, Mouse model
Abstract

Publisher Copyright: © 2022 The Authors Silver (nAg) and titanium dioxide (nTiO2) nanoparticles improve texture, flavour or anti-microbial properties of various food products and packaging materials. Despite their increased oral exposure, their potential toxicities in the dysfunctional intestine are unclear. Here, the effects of ingested nAg or nTiO2 on inflamed colon were revealed in a mouse model of chemical-induced acute ulcerative colitis. Mice (eight/group) were exposed to nAg or nTiO2 by oral gavage for 10 consecutive days. We characterized disease phenotypes, histology, and alterations in colonic transcriptome (RNA sequencing) and gut microbiome (16S sequencing). Oral exposure to nAg caused only minor changes in phenotypic hallmarks of colitic mice but induced extensive responses in gene expression enriching processes of apoptotic cell death and RNA metabolism. Instead, ingested nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila. Overall, nAg and nTiO2 induce dissimilar immunotoxicological changes at the molecular and microbiome level in the context of colon inflammation. The results provide valuable information for evaluation of utilizing metallic nanoparticles in food products for the vulnerable population.

Published
2022

42. Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation

Author

Fyhrquist, Nanna, Ruokolainen, Lasse, Suomalainen, Alina, Lehtimäki, Sari, Veckman, Ville, Vendelin, Johanna, Karisola, Piia, Lehto, Maili, Savinko, Terhi, Jarva, Hanna, Kosunen, Timo U., Corander, Jukka, Auvinen, Petri, Paulin, Lars, von Hertzen, Leena, Laatikainen, Tiina, Mäkelä, Mika, Haahtela, Tari, Greco, Dario, Hanski, Ilkka, and Alenius, Harri

Published
2014
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46. Contributors

Author

Alenius, Harri, primary, Beezhold, Don, additional, Bergamaschi, Enrico, additional, Boraschi, Diana, additional, Bouwmeester, Hans, additional, Campagnolo, Luisa, additional, Chen, Chunying, additional, de Jong, Wim H., additional, Doak, Shareen H., additional, Docter, Dominic, additional, Donaldson, Ken, additional, Duffin, Rodger, additional, Duschl, Albert, additional, Dusinska, Maria, additional, Epa, Vidana, additional, Fadeel, Bengt, additional, Larese Filon, Francesca, additional, Guseva Canu, Irina, additional, Gwinn, Maureen R., additional, Hirose, Akihiro, additional, Hougaard, Karin S., additional, Jepson, Mark A., additional, Kanno, Jun, additional, Knauer, Shirley K., additional, Landsiedel, Robert, additional, Le, Tu C., additional, Liu, Ying, additional, Lu, Xuefei, additional, Magrini, Andrea, additional, Mattsson, Mats-Olof, additional, Mech, Agnieszka, additional, Mills, Nicholas L., additional, Monteiro-Riviere, Nancy A., additional, Pietroiusti, Antonio, additional, Poland, Craig A., additional, Prina-Mello, Adriele, additional, Raftis, Jennifer B., additional, Rasmussen, Kirsten, additional, Rauscher, Hubert, additional, Rundén-Pran, Elise, additional, Sauer, Ursula G., additional, Savolainen, Kai, additional, Schnekenburger, Jürgen, additional, Shurin, Galina V., additional, Shurin, Michael R., additional, Shvedova, Anna A., additional, Simkó, Myrtill, additional, Sokull-Klüttgen, Birgit, additional, Stauber, Roland H., additional, Tran, Lang, additional, Westmeier, Dana, additional, Winkler, Dave, additional, Yokel, Robert A., additional, Yu, Il Je, additional, Zhu, Tao, additional, and Zhu, Yong, additional

Published
2017
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49. Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma

Author

Ndika, Joseph, Karisola, Piia, Lahti, Vilma, Fyhrquist, Nanna, Laatikainen, Tiina, Haahtela, Tari, and Alenius, Harri

Subjects
General Medicine
Abstract

BackgroundPreviously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.ObjectiveHere, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.MethodsGenome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.ResultsFinnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < −0.5) and Micrococcus (R < −0.5).ConclusionIn Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.

Published
2022

50. A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles : Evidence from Transcriptomics Studies

Author

Wang, Shuyuan, Alenius, Harri, El-Nezami, Hani, Karisola, Piia, HUMI - Human Microbiome Research, and University of Helsinki

Subjects
Arabidopsis thaliana, titanium dioxide, TITANIUM-DIOXIDE NANOPARTICLES, COATED SILVER NANOPARTICLES, elegans, ENVIRONMENTALLY RELEVANT CONCENTRATIONS, 116 Chemical sciences, technology, industry, and agriculture, ZINC-OXIDE NANOPARTICLES, zinc oxide, engineered metal nanoparticles, IN-VITRO, zebrafish, CARBON NANOTUBES, LONG-TERM EXPOSURE, transcriptomics, DNA-DAMAGE, animal models (in vivo), cell cultures (in vitro), OXIDATIVE STRESS, (eco)toxicology, GENE-EXPRESSION
Abstract

Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) have attracted a great deal of attention due to their excellent electrical, optical, whitening, UV-adsorbing and bactericidal properties. The extensive production and utilization of these NPs increases their chances of being released into the environment and conferring unintended biological effects upon exposure. With the increasingly prevalent use of the omics technique, new data are burgeoning which provide a global view on the overall changes induced by exposures to NPs. In this review, we provide an account of the biological effects of ZnO and TiO2 NPs arising from transcriptomics in in vivo and in vitro studies. In addition to studies on humans and mice, we also describe findings on ecotoxicology-related species, such as Danio rerio (zebrafish), Caenorhabditis elegans (nematode) or Arabidopsis thaliana (thale cress). Based on evidence from transcriptomics studies, we discuss particle-induced biological effects, including cytotoxicity, developmental alterations and immune responses, that are dependent on both material-intrinsic and acquired/transformed properties. This review seeks to provide a holistic insight into the global changes induced by ZnO and TiO2 NPs pertinent to human and ecotoxicology.

Published
2022

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