Tumour necrosis factor alpha enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells Journal Article

Local Library Link: Find It @ Loyola

Authors: Langert, K. A.; Von Zee, C. L.; Stubbs, E. B., Jr
Article Title: Tumour necrosis factor alpha enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells
Abstract: Recruitment and trafficking of autoreactive leucocytes across the BNB (blood-nerve barrier) is an early pathological insult in GBS (Guillain-Barre syndrome), an aggressive autoimmune disorder of the PNS (peripheral nervous system). Whereas the aetiology and pathogenesis of GBS remain unclear, pro-inflammatory cytokines, including TNFalpha (tumour necrosis factor alpha), are reported to be elevated early in the course of GBS and may initiate nerve injury by activating the BNB. Previously, we reported that disrupting leucocyte trafficking in vivo therapeutically attenuates the course of an established animal model of GBS. Here, PNMECs (peripheral nerve microvascular endothelial cells) that form the BNB were harvested from rat sciatic nerves, immortalized by SV40 (simian virus 40) large T antigen transduction and subsequently challenged with TNFalpha. Relative changes in CCL2 (chemokine ligand 2) and ICAM-1 (intercellular adhesion molecule 1) expression were determined. We report that TNFalpha elicits marked dose- and time-dependent increases in CCL2 and ICAM-1 mRNA and protein content and promotes secretion of functional CCL2 from immortalized and primary PNMEC cultures. TNFalpha-mediated secretion of CCL2 promotes, in vitro, the transendothelial migration of CCR2-expressing THP-1 monocytes. Increased CCL2 and ICAM-1 expression in response to TNFalpha may facilitate recruitment and trafficking of autoreactive leucocytes across the BNB in autoimmune disorders, including GBS.
Journal Title: ASN neuro
Volume: 5
Issue: 1
ISSN: 1759-0914
Publisher: Unknown  
Journal Place: England
Date Published: 2013
Start Page: e00104
Language: eng
DOI/URL:

10.1042/AN20120048

10.1042/AN20120048
Notes: ID: 13089; GR: 1R03NS061033/NS/NINDS NIH HHS/United States; JID: 101507115; OID: NLM: PMC3565377; epublish