{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T01:50:13Z","timestamp":1780365013477,"version":"3.54.1"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danube Allergy Research Cluster projects P06 and P09 funded by the Country of Lower Austria"},{"name":"Karl Landsteiner University of Health Sciences, Krems, Austria"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pollen, in addition to allergens, comprise low molecular weight components (LMC) smaller than 3 kDa. Emerging evidence indicates the relevance of LMC in allergic immune responses. However, the interaction of birch pollen (BP)-derived LMC and epithelial cells has not been extensively studied. We investigated epithelial barrier modifications induced by exposure to BP LMC, using the human bronchial epithelial cell line 16HBE14o-. Epithelial cell monolayers were apically exposed to the major BP allergen Bet v 1, aqueous BP extract or BP-derived LMC. Barrier integrity after the treatments was monitored by measuring transepithelial electrical resistance at regular intervals and by using the xCELLigence Real-Time Cell Analysis system. The polarized release of cytokines 24 h following treatment was measured using a multiplex immunoassay. Epithelial barrier integrity was significantly enhanced upon exposure to BP LMC. Moreover, BP LMC induced the repair of papain-mediated epithelial barrier damage. The apical release of CCL5 and TNF-\u03b1 was significantly reduced after exposure to BP LMC, while the basolateral release of IL-6 significantly increased. In conclusion, the results of our study demonstrate that BP-derived LMC modify the physical and immunological properties of bronchial epithelial cells and thus regulate airway epithelial barrier responses.<\/jats:p>","DOI":"10.3390\/ijms25137374","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of Bronchial Epithelial Barrier Integrity by Low Molecular Weight Components from Birch Pollen"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-5875","authenticated-orcid":false,"given":"Srinidhi","family":"Sudharson","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Hospital Sankt Poelten, Karl Landsteiner University of Health Sciences, 3100 Sankt Poelten, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9641-0244","authenticated-orcid":false,"given":"Tanja","family":"Kalic","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Sankt Poelten, Karl Landsteiner University of Health Sciences, 3100 Sankt Poelten, Austria"},{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5981-1607","authenticated-orcid":false,"given":"Julia","family":"Eckl-Dorna","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Lengger","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2022-8689","authenticated-orcid":false,"given":"Heimo","family":"Breiteneder","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3745-1414","authenticated-orcid":false,"given":"Christine","family":"Hafner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Sankt Poelten, Karl Landsteiner University of Health Sciences, 3100 Sankt Poelten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salazar, F., and Ghaemmaghami, A.M. (2013). Allergen recognition by innate immune cells: Critical role of dendritic and epithelial cells. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00356"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gandhi, V.D., and Vliagoftis, H. (2015). Airway epithelium interactions with aeroallergens: Role of secreted cytokines and chemokines in innate immunity. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00147"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.immuni.2015.07.007","article-title":"Barrier Epithelial Cells and the Control of Type 2 Immunity","volume":"43","author":"Hammad","year":"2015","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"020","DOI":"10.1186\/s13601-020-00341-y","article-title":"Initiating pollen sensitization\u2014Complex source, complex mechanisms","volume":"10","author":"Pointner","year":"2020","journal-title":"Clin. Transl. Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guryanova, S.V., Finkina, E.I., Melnikova, D.N., Bogdanov, I.V., Bohle, B., and Ovchinnikova, T.V. (2022). How Do Pollen Allergens Sensitize?. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.900533"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13854","DOI":"10.1111\/pai.13854","article-title":"EAACI Molecular Allergology User\u2019s Guide 2.0","volume":"34","author":"Dramburg","year":"2023","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Breiteneder, H., and Kraft, D. (2023). The History and Science of the Major Birch Pollen Allergen Bet v 1. Biomolecules, 13.","DOI":"10.3390\/biom13071151"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jaci.2014.04.015","article-title":"Do lipids influence the allergic sensitization process?","volume":"134","author":"Bublin","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1062316","DOI":"10.1080\/15476286.2015.1062316","article-title":"Low molecular weight components of pollen alter bronchial epithelial barrier functions","volume":"3","author":"Blume","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.molimm.2019.04.029","article-title":"Fish-derived low molecular weight components modify bronchial epithelial barrier properties and release of pro-inflammatory cytokines","volume":"112","author":"Kalic","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.jaci.2010.12.1082","article-title":"Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell-primed T(H) cell responses","volume":"127","author":"Gilles","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/all.12642","article-title":"Pollen-derived adenosine is a necessary cofactor for ragweed allergy","volume":"70","author":"Wimmer","year":"2015","journal-title":"Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1111\/cea.12739","article-title":"Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo","volume":"46","author":"Beck","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez Rold\u00e1n, N., Engel, R., D\u00fcpow, S., Jakob, K., Koops, F., Orinska, Z., Vigor, C., Oger, C., Galano, J.M., and Durand, T. (2019). Lipid Mediators From Timothy Grass Pollen Contribute to the Effector Phase of Allergy and Prime Dendritic Cells for Glycolipid Presentation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00974"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1067\/mai.2002.124655","article-title":"Lipid mediators from pollen act as chemoattractants and activators of polymorphonuclear granulocytes","volume":"109","author":"Kasche","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.jaci.2004.03.011","article-title":"Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators","volume":"113","author":"Feussner","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/jid.2015.58","article-title":"Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL\/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation","volume":"135","author":"Stremnitzer","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11245","DOI":"10.1038\/s41598-018-29689-9","article-title":"The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice","volume":"8","author":"Secher","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1084\/jem.20041065","article-title":"Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization","volume":"201","author":"Mariani","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1111\/all.12707","article-title":"Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells","volume":"70","author":"Oeder","year":"2015","journal-title":"Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1042\/BJ20130413","article-title":"Secret of the major birch pollen allergen Bet v 1: Identification of the physiological ligand","volume":"457","author":"Hoffmann","year":"2014","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Kerien\u0117, I., \u0160aulien\u0117, I., \u0160ukien\u0117, L., Jud\u017eentien\u0117, A., Ligor, M., and Buszewski, B. (2023). Patterns of Phenolic Compounds in Betula and Pinus Pollen. Plants, 12.","DOI":"10.3390\/plants12020356"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1016\/j.jaci.2020.03.005","article-title":"The role of eosinophils in chronic spontaneous urticaria","volume":"145","author":"Altrichter","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jaci.2013.03.005","article-title":"TNF-\u03b1-mediated bronchial barrier disruption and regulation by src-family kinase activation","volume":"132","author":"Hardyman","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31263","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"966","DOI":"10.7150\/ijbs.6996","article-title":"Interleukin-8 regulates endothelial permeability by down-regulation of tight junction but not dependent on integrins induced focal adhesions","volume":"9","author":"Yu","year":"2013","journal-title":"Int. J. Biol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tian, L., Li, Y., Zhang, J., Chang, R., Li, J., and Huo, L. (2018). IL-9 promotes the pathogenesis of ulcerative colitis through STAT3\/SOCS3 signaling. Biosci. Rep., 38.","DOI":"10.1042\/BSR20181521"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e983777","DOI":"10.4161\/21688370.2014.983777","article-title":"IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis","volume":"3","author":"Gerlach","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.jaci.2012.05.052","article-title":"Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-\u03b3 and IL-4","volume":"130","author":"Soyka","year":"2012","journal-title":"J. Allergy Clin. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7374\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:10:32Z","timestamp":1760109032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7374"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":29,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137374"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137374","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]}}}