Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation

Autor: Paul Jennings, Jordan Kountchev, Sonia Aydin, Daniel H. Sturn, Michael Joannidis, Klaudija Bijuklic, Walter Pfaller, Josef R. Patsch, Julia Hasslacher
Přispěvatelé: Molecular and Computational Toxicology, AIMMS
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Lipopolysaccharides
Pathology
Time Factors
Physiology
medicine.medical_treatment
Kidney Tubules
Proximal
Leukocytes
Electric Impedance
Non-U.S. Gov't
Skin
Nephritis
Chemotaxis
Research Support
Non-U.S. Gov't
Proximal
Chemotaxis
Leukocyte
Kidney Tubules
medicine.anatomical_structure
Cytokine
Tumor necrosis factor alpha
medicine.symptom
medicine.medical_specialty
Endothelium
Mononuclear
Inflammation
Biology
Research Support
Microcirculation
Cell Line
SDG 3 - Good Health and Well-being
medicine
Journal Article
Humans
Comparative Study
Interleukin 8
Interleukin 6
Cell Shape
Interleukin-6
Tumor Necrosis Factor-alpha
Interleukin-8
Endothelial Cells
Epithelial Cells
Cell Biology
Leukocyte
Epithelium
Coculture Techniques
alpha-MSH
Immunology
biology.protein
Leukocytes
Mononuclear
Nephritis
Interstitial
Interstitial
Zdroj: Bijuklic, K, Jennings, P, Kountchev, J, Hasslacher, J, Aydin, S, Sturn, D, Pfaller, W, Patsch, J R & Joannidis, M 2007, ' Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation ', American Journal of Physiology : Cell Physiology, vol. 293, no. 1, pp. C486-92 . https://doi.org/10.1152/ajpcell.00419.2006
American Journal of Physiology : Cell Physiology, 293(1), C486-92. American Physiological Society
ISSN: 0363-6143
Popis: Interstitial inflammation has emerged as a key event in the development of acute renal failure. To gain better insight into the nature of these inflammatory processes, the interplay between tubular epithelial cells, endothelial cells, and neutrophils (PMN) was investigated. A coculture transmigration model was developed, composed of human dermal microvascular endothelial (HDMEC) and human renal proximal tubular cells (HK-2) cultured on opposite sides of Transwell growth supports. Correct formation of an endoepithelial bilayer was verified by light and electron microscopy. The model was used to study the effects of endotoxin (LPS), tumor necrosis factor (TNF)-alpha, and alpha-melanocyte-stimulating hormone (alpha-MSH) by measuring PMN migration and cytokine release. To distinguish between individual roles of microvascular endothelial and epithelial cells in transmigration processes, migration of PMN was investigated separately in HK-2 and HDMEC monolayers. Sequential migration of PMN through endothelium and epithelium could be observed and was significantly increased after proinflammatory stimulation with either TNF-alpha or LPS (3.5 +/- 0.58 and 2.76 +/- 0.64-fold vs. control, respectively). Coincubation with alpha-MSH inhibited the transmigration of PMN through the bilayer after proinflammatory stimulation with LPS but not after TNF-alpha. The bilayers produced significant amounts of IL-8 and IL-6 mostly released from the epithelial cells. Furthermore, alpha-MSH decreased LPS-induced IL-6 secretion by 30% but had no significant effect on IL-8 secretion. We established a transmigration model showing sequential migration of PMN across microvascular endothelial and renal tubular epithelial cells stimulated by TNF-alpha and LPS. Anti-inflammatory effects of alpha-MSH in this bilayer model are demonstrated by inhibition on PMN transmigration and IL-6 secretion.
Databáze: OpenAIRE
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