The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells

Abstract

Krajewska M. The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells. AbstractThe innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

“…The MAPK pathway is a key factor in regulating cisplatin-induced kidney damage and inflammation. Based on previous evidence, various biological responses have been associated with the activation of MAPKs, which can activate the MAPK pathway by producing oxidative stress and TNF-α in the kidney tissues [40]. In this study, we showed that there was an increased amount of the phosphorylated MAPK proteins in the kidneys of cisplatin-treated mice.…”

“…Oxidative stress is one of the key factors in the pathogenesis of cisplatin-treated renal injury [40]. Cells express a number of antioxidant enzymes (e.g., SOD, catalase, and GPx) to prevent the cell or tissue damage caused by the expression of antioxidant enzymes, in an attempt to decrease oxidative stress.…”

CTRP3 attenuates inflammation, oxidative and cell death in cisplatin induced HK-2 cells

“…The MAPK signaling pathways play an important role in regulating inflammation and apoptosis ( Nath, 2006 ; Zmonarski et al, 2019 ). Previous studies have reported that MAPK pathways are activated in cisplatin-induced AKI, and inhibition of MAPK pathways alleviate cisplatin-induced inflammation and apoptosis ( Sahu, Mahesh Kumar & Sistla, 2015 ).…”