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Sudha Swamynathan, Anil Tiwari, Chelsea Loughner, Nicholas Alexander, John Gnalian, Shivalingappa K Swamynathan; Secreted Ly-6/uPAR Related Protein-1 (SLURP1) modulates inflammation by influencing both neutrophils and endothelial cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3325.
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© ARVO (1962-2015); The Authors (2016-present)
The Secreted Ly-6/uPAR Related Protein-1 (SLURP1), abundantly expressed in the cornea and secreted into the tear film, serves as an immunomodulatory molecule. Previously, we demonstrated that SLURP1 interferes with binding of differentiated HL-60 neutrophils (dHL-60) to, and their transmigration through a confluent human umbilical vein endothelial cell (HUVEC) monolayer. Here, we examine the molecular mechanisms underlying these functions.
The effect of SLURP1 (expressed in E. coli and partially purified) on E-selectin expression was studied by QPCR and fluorescence-assisted cell sorting (FACS), and VE-Cadherin and b-catenin was studied by QPCR and immunofluorescent staining in tumor necrosis factor-α (TNF-α)-stimulated HUVEC. The effect of SLURP1 on fMLP-induced AKT phosphorylation, Actin polymerization and RhoA expression in dHL60 cells was examined by immunoblots and immunofluorescent staining. The effect of SLURP1 on L-Selectin expression during DMSO-induced differentiation of HL-60 was studied by FACS.
SLURP1 treatment of TNF-α-activated HUVEC resulted in increased retention of VE cadherin and b-catenin in cell junctions, and decreased nuclear localization of b-catenin. SLURP1 suppressed the TNF-α-induced upregulation of E-selectin expression by both QPCR and FACS. SLURP1 also suppressed fMLP-induced increase in AKT phosphorylation, actin polymerization and RhoA expression in dHL-60 cells. SLURP1 suppressed the expression of L-Selectin during DMSO-induced differentiation of HL-60 at 2, 4 and 6 days after DMSO addition.
SLURP1 (i) promotes endothelial cell layer integrity by suppressing the disruptive effect of TNF-a on VE-cadherin and b-catenin, and (ii) slows down neutrophil migration by suppressing AKT phosphorylation, RhoA expression and actin polymerization. Together, these results demonstrate that SLURP1 modulates inflammation by influencing both neutrophils and endothelial cells.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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