Mouse Anti-Human SELE Hybridoma [DM4]

The objective of this study was to determine the role of individual NFAT isoforms in TNF alpha-induced retinal leukostasis. To this end, human retinal microvascular endothelial cells (HRMEC) transfected with siRNA targeting individual NFAT isoforms were treated with TNF alpha, and qRT-PCR was used to examine the contribution of each isoform to the TNF alpha-induced upregulation of leukocyte adhesion proteins. This showed that NFATc1 siRNA increased ICAM1 expression, NFATc2 siRNA reduced CX3CL1, VCAM1, SELE, and ICAM1 expression, NFATc3 siRNA increased CX3CL1 and SELE expression, and NFATc4 siRNA reduced SELE expression. Transfected HRMEC monolayers were also treated with TNFa and assayed using a parallel plate flow chamber, and both NFATc2 and NFATc4 knockdown reduced TNF alpha-induced cell adhesion. The effect of isoform-specific knockdown on TNF alpha-induced cytokine production was also measured using protein ELISAs and conditioned cell culture medium, and showed that NFATc4 siRNA reduced CXCL10, CXCL11, and MCP-1 protein levels. Lastly, the CN/NFAT-signaling inhibitor INCA-6 was shown to reduce TNF alpha-induced retinal leukostasis in vivo. Together, these studies show a clear role for NFAT-signaling in TNF alpha-induced retinal leukostasis, and identify NFATc2 and NFATc4 as potentially valuable therapeutic targets for treating retinopathies in which TNFa plays a pathogenic role.

The Sele river plain is located along the western Tyrrhenian margin of the southern Apennine Chain and is confined seaward by a straight sandy coast formed during the Last Interglacial and the Holocene. The coastal plain is characterised by beach-dune ridges which interfinger landwards with lagoon and fluvio-palustrine deposits. This belt, which progressively grew up, represents the evolution of a barrier-lagoon system alternatively shifting landwards and seawards. The knowledge on the Holocene evolution of the Sele river coastal plain, along the coast of the Poseidonia-Paestum archaeological area, was improved by the drilling of two new cores and the collection of several archaeo-tephro-stratigraphic data. The area experienced the Holocene marine transgression which cut high cliffs in the travertine deposits. During the second half of the Holocene, the shoreline shifted seawards and a lagoon-beach bar system (Fossa Lupata-Laura) formed. The archaeological remains (VI cent. b.c.) and the Agnano Monte Spina tephra layer (4.1 ky BP) constrain chronologically this morpho-sedimentary system. After the VI cent. b.c., and mostly after the deposition of the 79 a.d. tephra layer, the shoreline shifted seawards and an additional beach ridge formed, while the flat area at the back (Fossa Lupata) was rapidly aggraded and dried up.