{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:46:48Z","timestamp":1787017608254,"version":"build-2736575974"},"reference-count":29,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:p>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)-\u03b1, and \u03b1-melanocyte-stimulating hormone (\u03b1-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-\u03b1 or LPS (3.5 \u00b1 0.58 and 2.76 \u00b1 0.64-fold vs. control, respectively). Coincubation with \u03b1-MSH inhibited the transmigration of PMN through the bilayer after proinflammatory stimulation with LPS but not after TNF-\u03b1. The bilayers produced significant amounts of IL-8 and IL-6 mostly released from the epithelial cells. Furthermore, \u03b1-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-\u03b1 and LPS. Anti-inflammatory effects of \u03b1-MSH in this bilayer model are demonstrated by inhibition on PMN transmigration and IL-6 secretion.<\/jats:p>","DOI":"10.1152\/ajpcell.00419.2006","type":"journal-article","created":{"date-parts":[[2007,4,11]],"date-time":"2007-04-11T20:25:35Z","timestamp":1176323135000},"page":"C486-C492","source":"Crossref","is-referenced-by-count":41,"title":["Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation"],"prefix":"10.1152","volume":"293","author":[{"given":"Klaudija","family":"Bijuklic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Jennings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Kountchev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hasslacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Aydin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sturn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Pfaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef R.","family":"Patsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Joannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Bijuklic K\n                      , Sturn DH, Jennings P, Kountchev J, Pfaller W, Wiedermann CJ, Patsch JR, Joannidis M.\n                      Mechanisms of neutrophil transmigration across renal proximal tubular HK-2 cells.\n                      Cell Physiol Biochem\n                      17\n                      : 233\u2013244, 2006.","DOI":"10.1159\/000094128"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Bittleman DB\n                      , Casale TB.\n                      Interleukin-8 mediates interleukin-1 alpha-induced neutrophil transcellular migration.\n                      Am J Respir Cell Mol Biol\n                      13\n                      : 323\u2013329, 1995.","DOI":"10.1165\/ajrcmb.13.3.7654388"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Buffey J\n                      , Thody AJ, Bleehen SS, Mac NS.\n                      Alpha-melanocyte-stimulating hormone stimulates protein kinase C activity in murine B16 melanoma.\n                      J Endocrinol\n                      133\n                      : 333\u2013340, 1992.","DOI":"10.1677\/joe.0.1330333"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Catania A\n                      , Rajora N, Capsoni F, Minonzio F, Star RA, Lipton JM.\n                      The neuropeptide alpha-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro.\n                      Peptides\n                      17\n                      : 675\u2013679, 1996.","DOI":"10.1016\/0196-9781(96)00037-X"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Chiao H\n                      , Kohda Y, McLeroy P, Craig L, Housini I, Star RA.\n                      Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats.\n                      J Clin Invest\n                      99\n                      : 1165\u20131172, 1997.","DOI":"10.1172\/JCI119272"},{"key":"R6","doi-asserted-by":"crossref","unstructured":"Coxon A\n                      , Tang T, Mayadas TN.\n                      Cytokine-activated endothelial cells delay neutrophil apoptosis in vitro and in vivo. A role for granulocyte\/macrophage colony-stimulating factor.\n                      J Exp Med\n                      190\n                      : 923\u2013934, 1999.","DOI":"10.1084\/jem.190.7.923"},{"key":"R7","doi-asserted-by":"crossref","unstructured":"Daffern PJ\n                      , Jagels MA, Hugli TE.\n                      Multiple epithelial cell-derived factors enhance neutrophil survival. 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2002.","DOI":"10.1097\/01.ASN.0000024436.00520.D8"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Kohda Y\n                      , Chiao H, Star RA.\n                      alpha-Melanocyte-stimulating hormone and acute renal failure.\n                      Curr Opin Nephrol Hyperten\n                      7\n                      : 413\u2013417, 1998.","DOI":"10.1097\/00041552-199807000-00011"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Lechner J\n                      , Krall M, Netzer A, Radmayr C, Ryan MP, Pfaller W.\n                      Effects of interferon alpha-2b on barrier function and junctional complexes of renal proximal tubular LLC-PK1 cells.\n                      Kidney Int\n                      55\n                      : 2178\u20132191, 1999.","DOI":"10.1046\/j.1523-1755.1999.00487.x"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Linas SL\n                      , Repine JE.\n                      Endothelial cells regulate proximal tubule epithelial cell sodium transport.\n                      Kidney Int\n                      55\n                      : 1251\u20131258, 1999.","DOI":"10.1046\/j.1523-1755.1999.00360.x"},{"key":"R17","unstructured":"MacNeil S\n                      , Dobson J, Bleehen SS, Buffey JA.\n                      MSH increases intracellular calcium in melanoma cells.\n                      Br J Dermol\n                      123\n                      : 828\u2013834, 1990."},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Mul FP\n                      , Zuurbier AE, Janssen H, Calafat J, van Wetering S, Hiemstra PS, Roos D, Hordijk PL.\n                      Sequential migration of neutrophils across monolayers of endothelial and epithelial cells.\n                      J Leukoc Biol\n                      68\n                      : 529\u2013537, 2000.","DOI":"10.1189\/jlb.68.4.529"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Pardi R\n                     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Dependence on a CD11b\/CD18-mediated event and enhanced efficiency in physiological direction.\n                      J Clin Invest\n                      88\n                      : 1605\u20131612, 1991.","DOI":"10.1172\/JCI115473"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Parkos CA\n                      .\n                      Cell adhesion and migration. I. 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