{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:46:46Z","timestamp":1761540406592},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2255,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In inflammatory kidney diseases procoagulatory activity (PCA) becomes evident. Glomerular fibrin deposits and capillary microthrombi are histopathological hallmarks in most forms of glomerulonephritis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Therefore in this study the expression of tissue factor (TF) as the main inducer of thrombogenesis was examined in cultured human mesangial cells (MC) in response to proinflammatory stimuli such as interleukin\u20101 (IL\u20101\u03b2), tumour necrosis factor alpha (TNF\u2010\u03b1) and lipopolysaccharide (LPS). Also main signalling pathways were investigated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>IL\u20101\u03b2, TNF\u2010\u03b1 and LPS induced TF in MC in a time and dose dependent manner on mRNA and protein levels. Highest activity was found after 12 h of stimulation. Induction of TF was completely blockable by BAPTA\u2010AM, a chelator of intracellular [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> as well as calphostin, a protein kinase C (PKC) inhibitor. Activation of the protein kinase A (PKA) pathway had no influence on basal TF expression, but down\u2010regulated cytokine\u2010induced TF. The PKA blocker, KT5720, increased TF formation significantly. Since TF exerts its activity primarily on the surface of cells and after release of encrypted receptors we further tested TF activity in MC supernatants. IL\u20101\u03b2 did not significantly increase TF activity in supernatants of intact cells. However, when MC were rendered apoptotic by oxidative metabolites, IL\u20101\u03b2 treated MC released highly stimulated TF activity into the supernatants, suggesting that a paracrine activation of the coagulatory cascade can take place under such conditions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inflammatory mediators up\u2010regulate TF expression in MC by a PKC dependent pathway whereas PKA can serve as a negative feed\u2010back link. Apoptosis of inflammatory MC may trigger to spread PCA.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>137<\/jats:bold>, 1116\u20131124. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704967\">10.1038\/sj.bjp.0704967<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704967","type":"journal-article","created":{"date-parts":[[2002,11,12]],"date-time":"2002-11-12T18:47:25Z","timestamp":1037126845000},"page":"1116-1124","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Protein kinase C (PKC) dependent induction of tissue factor (TF) by mesangial cells in response to inflammatory mediators and release during apoptosis"],"prefix":"10.1111","volume":"137","author":[{"given":"Detlef","family":"Lang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Terstesse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Dohle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Bangen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Banas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Gerd","family":"Pauels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.81.2.134"},{"key":"e_1_2_7_3_1","first-page":"37","article-title":"Mechanism of tissue factor activation on cells","volume":"9","author":"BACH R.R.","year":"1998","journal-title":"Blood Coag. 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