title: IL-33 and IL-4 impair barrier functions of human vascular endothelium via different mechanisms.
abstract: The vascular endothelium forms a barrier that controls flow of solutes and proteins and the entry of leukocytes into tissue. Injured tissue releases IL-33, which then alarms the immune system and attracts Th2 cells, thus increasing local concentration of IL-4. The aim of the study was to assess the influence of IL-33 and IL-4 on barrier functions of the human endothelium, expression of tight and adherent junction proteins, apoptosis and adhesive molecule surface expression in human endothelium in order to describe the mechanism of this effect. IL-33 and IL-4 decreased endothelial integrity and increased permeability. When added together, both cytokines lowered the endothelial integrity twice as much as used alone. This effect was accompanied by the down-regulation of occludin and VE-cadherin mRNA expression. Additionally, IL-4, but not IL-33, induced cell apoptosis. Both IL-33 and IL-4 showed the additive potency to down-regulate VE-cadherin mRNA expression. IL-33, unlike IL-4, increased the surface expression of ICAM-1, but not PECAM-1 in endothelial cells. Our results indicate that IL-33 may reversibly destabilize the endothelial barrier, thus accelerating the supply with immunomodulators and assisting leukocytes to reach wounded tissue. However, extended and less-controlled down-regulation of endothelial barrier, which may be a consequence of IL-33-initiated, but in fact IL-4-induced apoptosis of endothelial cells, may be deleterious and may eventually lead to the aggravation of inflammatory processes and the prolongation of tissue dysfunction.
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Kniaziewicza 1/5 Str., 91-347 Lodz, Poland. Electronic address: mchalubinski@op.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Chalubinski
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Kniaziewicza 1/5 Str., 91-347 Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wojdan
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Kniaziewicza 1/5 Str., 91-347 Lodz, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Luczak
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Kniaziewicza 1/5 Str., 91-347 Lodz, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Gorzelak
authors.affiliation: Immunopathology and Genetics Laboratory, Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland, Sporna 36/50 Str., 91-738 Lodz, Poland; Department of Clinical Genetics, Medical University of Lodz, Poland, Sterlinga 1/3 Str., 90-425 Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.affiliation: Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gajewski
authors.affiliation: Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rudnicka
authors.affiliation: Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chmiela
authors.affiliation: Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Medical University of Lodz, Kniaziewicza 1/5 Str., 91-347 Lodz, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Broncel
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D000067596:Interleukin-33 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D018799:Intercellular Adhesion Molecule-1; D000067596:Interleukin-33; D015847:Interleukin-4; D062793:Occludin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000099152:Cadherin 5; C573420:ICAM1 protein, human; C506536:IL33 protein, human; C508598:IL4 protein, human; C568985:OCLN protein, human
keywords: Barrier functions; Endothelium; IL-33; IL-4; Tight junctions; Tissue injury