title: Endogenous TGF-β activity limits TSLP expression in the intervertebral disc tissue by suppressing NF-κB activation.
abstract: Thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is highly expressed in herniated disc (HD) tissue and may act as a key molecule for the initiation of macrophage recruitment into the tissue and natural resorption of HD. However, it remains unclear how TSLP expression is regulated in the intervertebral discs. This study showed that expression of TSLP and phosphorylated NF-κB in HD tissue samples was inversely correlated with expression of phosphorylated Smad2/3 (an indicator of active TGF-β signaling) and vice versa in posterior lumbar spinal fusion samples. The pharmacological blockades of endogenous TGF-β activity induced TSLP expression in mouse intervertebral disc tissue culture, which was inhibited by NF-κB inhibitors. Additionally, phosphorylation of Smad2/3 was constitutively detected in mouse intervertebral disc tissue in the steady states. Collectively, these results suggest that endogenous TGF-β activity limits TSLP expression in intervertebral disc tissue in the steady states by suppressing NF-κB activation. The findings reveal a regulatory mechanism how TSLP expression is induced in the intervertebral disc tissue and suggest a novel role of TGF-β in maintaining the homeostasis of intervertebral disc tissue.
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohba
authors.forename: Takashi
authors.initials: T
authors.lastname: Ando
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Kensuke
authors.initials: K
authors.lastname: Koyama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Haro
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D023421:Models, Animal; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D000094632:Thymic Stromal Lymphopoietin