IL-10 delays the degeneration of intervertebral discs by suppressing the p38 MAPK signaling pathway

被引:65
作者
Ge, Jun [1 ]
Yan, Qi [1 ]
Wang, Yingjie [1 ]
Cheng, Xiaoqiang [1 ]
Song, Dawei [1 ]
Wu, Cenhao [1 ]
Yu, Hao [1 ]
Yang, Huilin [1 ]
Zou, Jun [1 ]
机构
[1] Soochow Univ, Dept Orthopaed Surg, Affiliated Hosp 1, 188 Shizi St, Suzhou 215006, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
IL-10; Intervertebral disc; Degeneration; p38; MAPK; TNF-ALPHA; INTERLEUKIN-10; CELLS; TRANSCRIPTION; INHIBITION; TARGET; INJURY;
D O I
10.1016/j.freeradbiomed.2019.12.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Objectives: The degeneration of intervertebral discs (IVD) is a risk factor for chronic low back pain. Anti-inflammation therapy could alleviate IVD degeneration. IL-10 is an important anti-inflammatory cytokine. However, the effect of IL-10 on IVD has not been fully revealed. The current study is to reveal the effect of IL-10 on IVD and its underlying mechanism. Methods: IL-1 beta was used to induce the degeneration of nucleus pulposus cells (NPCs). mRNA expression level was determined by qPCR. Protein expression level was determined by western blotting. Methylene blue was used to determined the expression of aggrecan. Immunocytochemical staining was used to determined the expression of collagen II. A rat caudal IVD degeneration model was established and used to evaluate the effect of IL-10 on IVD in vivo. Results: IL10 could alleviated NPC degeneration in both morphology and extracellular matrix. IL-10 could increase the mRNA expression of Collagen II, Sox-9, but decrease the mRNA expression of IL-1 beta, TNF alpha and Collagen X. IL-10 could also increase the protein level of Collagen II and aggrecan, but decrease that of Collagen X. Western blotting futher revealed the mechanism of the positive effect of IL-10 on IVD. IL-10 reduces phosphorylation level of p38 MAPK effectively. Rat caudal IVD degeneration model futher confirmed the positive effect of IL-10 on IVD degeneration and its mechanism in vivo. Conclusion: The current study demonstrates that exogenous IL-10 treatment can induce an anti-inflammatory response and inhibit p38 MAPK activation to delay IVD degeneration.
引用
收藏
页码:262 / 270
页数:9
相关论文
共 47 条
[1]  
[Anonymous], J CELL BIOCH
[2]  
[Anonymous], IMMUNITY
[3]  
[Anonymous], IMMUNOPHARMACOL IMMU
[4]  
[Anonymous], J BIOL CHEM
[5]   Activation of p38, ERK1/2 and NIK pathways is required for IL-1β and TNF-α-induced chemokine expression in human retinal pigment epithelial cells [J].
Bian, ZM ;
Elner, SG ;
Yoshida, A ;
Kunkel, SL ;
Su, J ;
Elner, VM .
EXPERIMENTAL EYE RESEARCH, 2001, 73 (01) :111-121
[6]   Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration [J].
Boos, N ;
Nerlich, AG ;
Wiest, I ;
von der Mark, K ;
Aebi, M .
HISTOCHEMISTRY AND CELL BIOLOGY, 1997, 108 (06) :471-480
[7]   Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: Identification of interleukin-10 as a major functional deactivator of human monocytes [J].
Brandtzaeg, P ;
Osnes, L ;
Ovstebo, R ;
Joo, GB ;
Westvik, AB ;
Kierulf, P .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (01) :51-60
[8]   Tangeretin suppresses IL-1β-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells [J].
Chen, Kuan-Hunq ;
Weng, Meng-Shih ;
Lin, Jen-Kun .
BIOCHEMICAL PHARMACOLOGY, 2007, 73 (02) :215-227
[9]   Ex vivo observation of human intervertebral disc tissue and cells isolated from degenerated intervertebral discs [J].
Ciapetti, Gabriela ;
Granchi, Donatella ;
Devescovi, Valentina ;
Leonardi, Elisa ;
Greggi, Tiziana ;
Di Silvestre, Mario ;
Baldini, Nicola .
EUROPEAN SPINE JOURNAL, 2012, 21 :S10-S19
[10]  
Clarke CJP, 1998, EUR J IMMUNOL, V28, P1719, DOI 10.1002/(SICI)1521-4141(199805)28:05<1719::AID-IMMU1719>3.0.CO