Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome
Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we a...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-07-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.701087/full |
id |
doaj-fca6b6ab36424a42a93b43e753c26ff2 |
---|---|
record_format |
Article |
spelling |
doaj-fca6b6ab36424a42a93b43e753c26ff22021-07-23T12:35:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.701087701087Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 InflammasomeFeng Zhao0Feng Zhao1Zhenye Guo2Fushan Hou3Wei Fan4Binqiang Wu5Zhonglai Qian6Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaIntervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by “M1” polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce “M1” polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What’s more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with “M1” polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment.https://www.frontiersin.org/articles/10.3389/fphar.2021.701087/fullmagnoflorinemacrophagesnucleus pulposus cellsintervertebral disc degenerationinflammatory responseNLRP3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Feng Zhao Feng Zhao Zhenye Guo Fushan Hou Wei Fan Binqiang Wu Zhonglai Qian |
spellingShingle |
Feng Zhao Feng Zhao Zhenye Guo Fushan Hou Wei Fan Binqiang Wu Zhonglai Qian Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome Frontiers in Pharmacology magnoflorine macrophages nucleus pulposus cells intervertebral disc degeneration inflammatory response NLRP3 |
author_facet |
Feng Zhao Feng Zhao Zhenye Guo Fushan Hou Wei Fan Binqiang Wu Zhonglai Qian |
author_sort |
Feng Zhao |
title |
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome |
title_short |
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome |
title_full |
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome |
title_fullStr |
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome |
title_full_unstemmed |
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome |
title_sort |
magnoflorine alleviates “m1” polarized macrophage-induced intervertebral disc degeneration through repressing the hmgb1/myd88/nf-κb pathway and nlrp3 inflammasome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-07-01 |
description |
Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by “M1” polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce “M1” polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What’s more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with “M1” polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment. |
topic |
magnoflorine macrophages nucleus pulposus cells intervertebral disc degeneration inflammatory response NLRP3 |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.701087/full |
work_keys_str_mv |
AT fengzhao magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT fengzhao magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT zhenyeguo magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT fushanhou magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT weifan magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT binqiangwu magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome AT zhonglaiqian magnoflorinealleviatesm1polarizedmacrophageinducedintervertebraldiscdegenerationthroughrepressingthehmgb1myd88nfkbpathwayandnlrp3inflammasome |
_version_ |
1721290215608287232 |