p38 MAPK Facilitates Crosstalk Between Endoplasmic Reticulum Stress and IL-6 Release in the Intervertebral Disc

Frontiers in Immunology
Olga KrupkovaKarin Wuertz-Kozak

Abstract

Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1β and TNF-α. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 µM) and knockdown of ER stress ...Continue Reading

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Citations

Jan 1, 2020·JOR Spine·Andrew BratsmanFlorent Elefteriou
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Jan 16, 2021·International Journal of Molecular Sciences·Laura BaumgartnerJérôme Noailly

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Methods Mentioned

BETA
protein-folding
PCR
enzyme-linked immunosorbent assay
FCS
ELISA
electrophoresis
Assay
transfection
ELISAs

Software Mentioned

STATISTICA
ImageJ
PASW
StatSoft
StatXact
GraphPad Prism

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