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Am J Physiol Renal Physiol. 2018 Apr 1;314(4):F630-F642. doi: 10.1152/ajprenal.00421.2017. Epub 2017 Dec 20.

Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells.

Author information

1
Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina , Charleston, South Carolina.
2
Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville , Louisville, Kentucky.
3
Division of Pathology and Laboratory Medicine, Department of Medicine, Medical University of South Carolina , Charleston, South Carolina.

Abstract

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

KEYWORDS:

IL-6; lupus nephritis; mesangial cells; neuraminidase

PMID:
29357434
PMCID:
PMC5966761
DOI:
10.1152/ajprenal.00421.2017
[Indexed for MEDLINE]
Free PMC Article

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