caa a22 4500 606236236 CHVBK 20210128101246.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2440-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2440-0 TNFα induces inflammatory stress response in microvascular endothelial cells via Akt- and P38 MAP kinase-mediated thrombospondin-1 expression [Elektronische Daten] [Arwa Fairaq, Anna Goc, Sandeep Artham, Harika Sabbineni, Payaningal Somanath] Tumor necrosis factor-α (TNFα) and thrombospondin-1 (TSP-1) are well-known mediators of inflammation. However, a causal relationship between TNFα stimuli and TSP-1 expression in endothelial cell stress, and the underlying mechanisms has not yet been investigated. In our study, human microvascular endothelial cells (hMEC) were treated with TNFα and analyzed for endothelial dysfunction, TSP-1 expression, and associated mechanisms. TNFα treatment induced a dose-dependent increase in TSP-1 expression in hMEC associated with increased endothelial permeability, apoptosis, and reduced proliferation. Whereas TNFα activated Akt, ERK, and P38 mitogen-activated protein kinase (P38 MAPK) simultaneously in hMEC, inhibitors of Akt and P38 MAPK, but not ERK blunted TNFα-induced TSP-1 expression. Silencing of NFκB gene had no significant effect on TNFα-induced TSP-1 expression. Our study demonstrates the novel role of TNFα in inducing inflammatory stress response in hMEC through Akt- and P38 MAPK-mediated expression of TSP-1, independent of NFκB signaling. Springer Science+Business Media New York, 2015 TNFα nationallicence TSP-1 nationallicence Inflammation nationallicence Endothelium nationallicence P38 MAPK nationallicence Akt nationallicence TNFα : Tumor necrosis factor-α nationallicence P38 MAPK : P38 mitogen-activated protein kinase nationallicence TSP-1 : Thrombospondin-1 nationallicence MAPK : Mitogen-activated protein kinase nationallicence ERK : Extracellular regulated kinase nationallicence hMEC : Human microvascular endothelial cells nationallicence ECIS : Electric cell-substrate impedance sensing nationallicence Fairaq Arwa Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut Goc Anna Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut Artham Sandeep Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut Sabbineni Harika Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut Somanath Payaningal Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 227-236 0300-8177 406:1-2<227 2015 406 11010 https://doi.org/10.1007/s11010-015-2440-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2440-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fairaq Arwa Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut NATIONALLICENCE 700 1- Goc Anna Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut NATIONALLICENCE 700 1- Artham Sandeep Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut NATIONALLICENCE 700 1- Sabbineni Harika Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut NATIONALLICENCE 700 1- Somanath Payaningal Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, HM1200, 30912, Augusta, GA, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 227-236 0300-8177 406:1-2<227 2015 406 11010