Cyclosporine-Induced Renal Injury Induces Toll-like Receptor and Maturation of Dendritic cells

Abstract

CsA-induced renal injury stimulates components of innate immunity, and this finding suggests close association between CsA-induced renal injury and activation of innate immunity.

Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell responses to hypoxic and toxic injury

“…For example, it has been suggested that TLR4, the most thoroughly studied member of the TLR family, is upregulated in the kidney 3-5 days postischemia (10,21) and after 28 days of cyclosporine treatment (13). However, recent observations from our laboratory indicate that increased TLR4 expression is not necessarily a generalized renal injury response (27).…”

“…The innate immune response/Toll-like receptor (TLR) pathway may be intimately involved in this process. TLRs are a family of ϳ11 plasma membrane glycoproteins that bind a variety of pathogen (e.g., endotoxins 3 TLR4; lipoteichoic acids 3 TLR2)-and nonpathogen (e.g., damaged RNA/DNA; heat shock proteins)-associated molecules (1,2,10,11,13,17,18,21). Once ligation occurs, downstream adaptor proteins (MyD88; Trif; Traf, NF-B) are recruited, culminating in increased cytokine and chemokine production (4,8,9).…”

Accumulation of CD4+T cells in the colon of CsA-treated mice following myeloablative conditioning and bone marrow transplantation

“…Radiation conditioning has been shown to induce the upregulation of transcription factors and proinflammatory cytokines (30,48,50). The other component of the SGVHD induction protocol, CsA, is a calcineurin inhibitor, which, as a class, mediates toxicities in several tissues via the induction of oxidative stress (13,46,47) and transcription factors, including NF-B (19,34,49) and inflammatory cytokines (16,32,37). Given the interrelationship between oxidative stress and cytokines and the induction of CAM expression (1,35,38,42,45), the potential exists that the unique interaction between pretransplant irradiation and CsA therapy could result in the generation of an inflammatory environment, leading to increased CAM expression and increased migration of effector cells into the colon of CsA-treated animals in the early post-BMT period.…”

Cellular crosstalk mechanism of Toll-like receptors in gingival overgrowth (Review)

“…Furthermore, cyclosporine-induced gingival overgrowth patients had a significantly higher number of TLR-4 expressing cells in the basal cell layer of the epithelium, as well as in connective tissue compared to healthy subjects (42). Lim et al (49) demonstrated an association between cyclosporine-induced renal injury and activation of innate immunity through TLR-2 and TLR-4 expression in renal tissues of rats and reported an increased TLR-2 and TLR-4 mRNA and protein expression in rat kidney. Another study by Suzuki et al (50) showed that TLR-mediated inflammatory responses were positively regulated by cyclosporine in human gingival fibroblasts.…”