Differential expression of p38 MAPK α, β, γ, δ isoforms in nucleus pulposus modulates macrophage polarization in intervertebral disc degeneration

Scientific Reports
Chen YangWen Yuan

Abstract

P38MAPK mediates cytokine induced inflammation in nucleus pulposus (NP) cells and involves in multiple cellular processes which are related to intervertebral disc degeneration (IDD). The aim of this study was to investigate the expression, activation and function of p38 MAPK isoforms (α,β, γ and δ) in degenerative NP and the effect of p38 activation in NP cells on macrophage polarization. P38 α, β and δ isoforms are preferential expressed, whereas the p38γ isoform is absent in human NP tissue. LV-sh-p38α, sh-p38β transfection in NP cells significantly decreased the ADAMTS-4,-5, MMP-13,CCL3 expression and restored collagen-II and aggrecan expression upon IL-1β stimulation. As compared with p38α and p38β, p38δ exhibited an opposite effect on ADAMTS-4,-5, MMP-13 and aggrecan expression in NP cells. Furthermore, the production of GM-CSF and IFNγ which were trigged by p38α or p38β in NP cells induced macrophage polarization into M1 phenotype. Our finding indicates that p38 MAPK α, β and δ isoform are predominantly expressed and activated in IDD. P38 positive NP cells modulate macrophage polarization through the production of GM-CSF and IFNγ. Hence, Our study suggests that selectively targeting p38 isoforms could ameliorate the infla...Continue Reading

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Citations

Dec 20, 2017·Frontiers in Immunology·Marie MonchauxKarin Wuertz-Kozak
Jan 23, 2018·Regenerative Medicine·Eduardo Anitua, Sabino Padilla
Mar 7, 2020·International Journal of Molecular Sciences·Carla CunhaRaquel M Goncalves
Aug 6, 2020·International Journal of Molecular Sciences·Ursula A Germann, John J Alam
Jul 26, 2018·Frontiers in Bioengineering and Biotechnology·Genglei ChuBin Li
Mar 15, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Junmin FuTiantai Zhang
May 19, 2021·Cell Chemical Biology·Kusal T G Samarasinghe, Craig M Crews
Aug 17, 2020·Cell Chemical Biology·Dhanusha A Nalawansha, Craig M Crews

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Methods Mentioned

BETA
transfection
immunoprecipitation
Flow Cytometric
confocal microscopy
flow cytometry

Software Mentioned

SPSS

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