July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Secreted Ly-6/uPAR Related Protein-1 (SLURP1) modulates inflammation by influencing both neutrophils and endothelial cells
Author Affiliations & Notes
  • Sudha Swamynathan
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Anil Tiwari
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Chelsea Loughner
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Nicholas Alexander
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • John Gnalian
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Shivalingappa K Swamynathan
    Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Sudha Swamynathan, Patent No: US 9731014 B2 (P); Anil Tiwari, None; Chelsea Loughner, None; Nicholas Alexander, None; John Gnalian, None; Shivalingappa Swamynathan, Patent No: US 9731014 B2 (P)
  • Footnotes
    Support  NIH Grant R01EY022898 (SKS), NEI Core Grant P30 EY08098, unrestricted grants from Research to Prevent Blindness and the Eye and Ear Foundation of Pittsburgh.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3325. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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