Aberrant regulation of the integrin very late antigen-4 in systemic lupus erythematosus.

Abstract:

:Integrin very late antigen-4 (VLA4) is induced during inflammation and can regulate monocyte migration. It has been implicated in atherogenesis, a significant concern in systemic lupus erythematosus (SLE). The aim of this study was to define VLA4 expression in SLE monocytes. Flow cytometry, reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry staining with confocal microscopy were used to evaluate VLA4 expression in SLE patients and controls. We found elevated expression of VLA4 in SLE patients with significantly increased VLA4 staining intracellularly compared to control. Exposure of control monocytes to SLE sera or immune complexes led to increased intracellular expression, and immune complexes were capable of driving redistribution of surface VLA4 to the cytoplasm. Therefore, VLA4 was found to be subject to complex regulation with SLE sera driving both RNA expression and redistribution of protein. Stimulation of SLE monocytes with a VLA4 ligand induced significant TNFα expression, confirming a functional effect. This behavior may contribute to increased atherosclerosis and monocyte infiltrates in end organs.

journal_name

Lupus

journal_title

Lupus

authors

Rahimi H,Maurer K,Song L,Akhter E,Petri M,Sullivan KE

doi

10.1177/0961203313475691

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

297-306

issue

3

eissn

0961-2033

issn

1477-0962

pii

22/3/297

journal_volume

22

pub_type

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