{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:27:12Z","timestamp":1789914432998,"version":"4.0.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"Alder Hey Children's Kidney Fund"},{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008241","name":"Alder Hey Children's NHS Foundation Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008241","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Alder Hey Charity"},{"DOI":"10.13039\/501100000836","name":"University Of Liverpool (Universidad de Liverpool)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000836","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health Research (NIHR) Alder Hey Clinical Research Facility for Experimental Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p>Lupus nephritis (LN) affects up to 80% of juvenile onset systemic lupus erythematosus patients, leading to end stage renal failure requiring dialysis or transplantation in 10\u201315%. Podocytes are specialized epithelial cells of the glomerulus known to be a key site of damage in glomerular diseases. However, their roles in LN have yet to be fully identified. This project aims to identify structural and functional roles of podocytes in an in vitro model of LN. Conditionally immortalized podocytes were treated with proinflammatory cytokines (IL-1\u03b2, TNF-\u03b1, IFN-\u03b1, and IFN-\u03b3) alone and in combination in an in vitro model of LN and were assessed for their structural and functional characteristics. Podocytes produce TNF-\u03b1, IL-6, IL-8, VEGF, granulocyte-monocyte colony stimulating factor (GM-CSF), and macrophage colony stimulating factor (M-CSF) at relatively low levels under basal conditions; stimulation with IL-1\u03b2 led to increased secretion of IL-6 ( P = 0.011), IL-8 ( P = 0.05), VEGF ( P = 0.02), and M-CSF ( P = 0.03). Stimulation with TNF-\u03b1 led to increased secretion of M-CSF ( P\u2009= 0.049) and stimulation with IFN-\u03b3 led to novel production of IL-10 ( P = 0.036) and interferon-\u03b3-inducible protein-10 ( P = 0.036). Podocytes demonstrate a reduction in the area covered by filamentous-actin in response to IL-1\u03b2 treatment within 1 h ( P = 0.011), which is restored by 24 h, associated with an increase in the level of intracellular calcium but not with increased cell death. Podocytes contribute to the inflammatory milieu in LN through cytokine\/chemokine secretion and respond to the inflammatory milieu via rearrangement of the actin cytoskeleton leading to effacement, a well-known method of protection against apoptosis in these cells. 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