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Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling.
Mol Immunol. 2017 11; 91:195-201.MI

Abstract

Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1β in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1β in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1β were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1β antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.

Authors+Show Affiliations

Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.Department of Galactophore, Shaanxi Provincial Cancer Hospital, Xi'an 710061, Shaanxi, PR China.Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, PR China.Department of Integrative Medical Biology, University of Umeå, 901 87 17 Umeå, Sweden.School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an 710061, Shaanxi, China. Electronic address: xiongguohospital@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28963928

Citation

Chang, Yanhai, et al. "Inflammatory Cytokine of IL-1β Is Involved in T-2 Toxin-triggered Chondrocyte Injury and Metabolism Imbalance By the Activation of Wnt/β-catenin Signaling." Molecular Immunology, vol. 91, 2017, pp. 195-201.
Chang Y, Wang X, Sun Z, et al. Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling. Mol Immunol. 2017;91:195-201.
Chang, Y., Wang, X., Sun, Z., Jin, Z., Chen, M., Wang, X., Lammi, M. J., & Guo, X. (2017). Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling. Molecular Immunology, 91, 195-201. https://doi.org/10.1016/j.molimm.2017.08.019
Chang Y, et al. Inflammatory Cytokine of IL-1β Is Involved in T-2 Toxin-triggered Chondrocyte Injury and Metabolism Imbalance By the Activation of Wnt/β-catenin Signaling. Mol Immunol. 2017;91:195-201. PubMed PMID: 28963928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling. AU - Chang,Yanhai, AU - Wang,Xiao, AU - Sun,Zhengming, AU - Jin,Zhankui, AU - Chen,Ming, AU - Wang,Xiaoqing, AU - Lammi,Mikko J, AU - Guo,Xiong, Y1 - 2017/09/30/ PY - 2017/06/18/received PY - 2017/08/20/revised PY - 2017/08/22/accepted PY - 2017/10/1/pubmed PY - 2017/10/27/medline PY - 2017/10/1/entrez KW - Cytotoxic injury KW - Inflammation KW - Kashin–Beck disease KW - Metabolism homeostasis KW - T-2 toxin KW - Wnt/β-catenin pathway SP - 195 EP - 201 JF - Molecular immunology JO - Mol. Immunol. VL - 91 N2 - Mycotoxin T-2 exerts a causative role in Kashin-Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1β in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1β in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1β were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1β antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/28963928/Inflammatory_cytokine_of_IL_1β_is_involved_in_T_2_toxin_triggered_chondrocyte_injury_and_metabolism_imbalance_by_the_activation_of_Wnt/β_catenin_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(17)30483-2 DB - PRIME DP - Unbound Medicine ER -