title: Interleukin-2 is upregulated in patients with a prolapsed lumbar intervertebral disc and modulates cell proliferation, apoptosis and extracellular matrix metabolism of human nucleus pulposus cells.
abstract: Previous studies have demonstrated that the expression levels of cytokines are increased in degenerated intervertebral disc tissues, and several cytokines are associated with the pathogenesis of intervertebral disc degeneration. However, the role of interleukin (IL)-2 in the cellular functions of intervertebral disc tissues remains unreported. The present study aimed to determine the expression levels of IL-2 in the nucleus pulposus (NP) tissues of patients with a prolapsed lumbar intervertebral disc; and to observe the changes in cell proliferation, apoptosis, extracellular matrix (ECM) metabolism and p38 mitogen-activated protein kinase (MAPK) signaling in human NP cells (HNPCs) following treatment with IL-2. The present study demonstrated that IL-2 expression levels were upregulated in the NP tissues of patients with a prolapsed lumbar intervertebral disc; and a subsequent MTT assay demonstrated that IL-2 inhibits the proliferation of HNPCs in a dose-dependent manner. Furthermore, as demonstrated by the increased protein expression levels of Fas cell surface death receptor and the induction of caspase-8 and caspase-3 activity, the death receptor pathway was activated by IL-2 in the HNPCs in order to promote cell apoptosis. In addition, IL-2 promoted ECM degradation in the HNPCs, as demonstrated by an increase in the expression levels of type I collagen, a disintegrin and metalloproteinase with thrombospondin motifs and matrix metalloproteinases, and decreased aggrecan and type II collagen expression levels. Furthermore, phosphorylated-p38 was significantly increased in the HNPCs following IL-2 treatment. In conclusion, the present study demonstrated that IL-2 inhibits cell proliferation, and induces cell apoptosis and ECM degradation, accompanied by the activation of p38 MAPK signaling in HNPCs. Therefore, IL-2 may be a potential therapeutic agent for the treatment of degenerative disc disease.
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China ; Department of Orthopedic Surgery, Zhangjiagang Hospital of Traditional Chinese Medicine, Zhangjiagang, Jiangsu 215600, P.R. China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Genlin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Dechun
authors.initials: D
authors.lastname: Geng
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
keywords: apoptosis; extracellular matrix metabolism; interleukin-2; nucleus pulposus cells; proliferation