Involvement of TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation

Abstract

T-2 toxin, a highly toxic type A monotrichothecene mycotoxin, has been found in many different types of cereals and is considered to be one of the most dangerous naturally occurring forms of food contamination. Globally, consuming grain-based food tainted with T-2 toxin poses significant risks to animal and human health. Prior research has indicated that the presence of T-2 toxin may lead to the demise of chondrocytes and the deterioration of the extracellular matrix of cartilage in degenerative bone and joint conditions, such as Kashin-Beck disease. However, the mechanisms by which T-2 toxin exerts its biological toxicity on the degradation of the extracellular matrix in cartilage are not well understood. In the current study, we found original results that demonstrate an upregulation of Toll-Like Receptors (TLR-2, TLR-4) and ESE-1 expression levels in the articular cartilage of a rat model subjected to T-2 toxin exposure. Furthermore, it was revealed that the exposure to T-2 toxin resulted in an increase in the expression of TLR-2, TLR-4, and ESE-1 in human C28/I2 chondrocytes. The findings of this study indicate that the increased expression of TLR-2, TLR-4, and ESE-1 may contribute to the development of degenerative osteoarthritic disease caused by T-2 toxin. Consistent with our hypotheses, we discovered that T-2 toxin increased the expression of MMP-1 and MMP-13 in human C28/I2 chondrocytes. We used a luciferase reporter gene assay to measure the activity of the ESE-1 promoter and transfected cells with plasmids encoding TLR-2 and TLR-4 to investigate their effects on this activity. TLR-2 and TLR-4 can activate ESE-1 transcriptional gene expression, and this expression is mediated through the NF-κB pathway, additional evidence is provided for the participation of the TLRs/NF-κB/ESE-1 signaling pathway in T-2 toxin-induced cartilage matrix degradation. Together, the findings indicated that the TLRs/NF-κB/ESE-1 signaling pathway played an essential part in T-2 toxin-induced cartilage matrix degradation.