Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyelonephritis, in which renal tubular epithelial cells are directly exposed to bacterial component, is a major predisposing cause of renal insufficiency. Although previous studies have suggested C-C chemokines are involved in the pathogenesis, the exact source and mechanisms of the chemokine secretion remain ambiguous. In this study, we evaluated the involvement of Toll-like receptors (TLRs) in C-C chemokine production by mouse primary renal tubular epithelial cells (MTECs). MTECs constitutively expressed mRNA for TLR1, 2, 3, 4, and 6, but not for TLR5 or 9. MTECs also expressed MD-2, CD14, myeloid differentiation factor 88, and Toll receptor-IL-1R domain-containing adapter protein/myeloid differentiation factor 88-adapter-like. Synthetic lipid A and lipoprotein induced monocyte chemoattractant protein 1 (MCP-1) and RANTES production in MTECs, which strictly depend on TLR4 and TLR2, respectively. In contrast, MTECs were refractory to CpG-oligodeoxynucleotide in chemokine production, consistently with the absence of TLR9. LPS-mediated MCP-1 and RANTES production in MTECs was abolished by NF-kappaB inhibition, but unaffected by extracellular signal-regulated kinase inhibition. In LPS-stimulated MTECs, inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase significantly decreased RANTES, but did not affect MCP-1 mRNA induction. Thus, MTECs have a distinct expression pattern of TLR and secrete C-C chemokines in response to direct stimulation with a set of bacterial components.
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PMID:Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. 1216 29

Toll-like receptors (TLR) are an emerging family of receptors that recognize pathogen-associated molecular patterns and promote the activation of leukocytes and intrinsic renal cells. Ligands of the TLR include exogenous microbial components such as LPS (TLR4), lipoproteins and peptidoglycans (TLR1, -2, -6), viral RNA (TLR3), bacterial and viral unmethylated cytosin-guanosin dinucleotide (CpG)-DNA (TLR9), and endogenous molecules including heat-shock proteins and extracellular matrix molecules. Upon stimulation, TLR induce expression of inflammatory cytokines or costimulatory molecules via the MyD88-dependent and MyD88-independent signaling pathways shared with the interleukin-1 receptors. TLR are differentially expressed on leukocyte subsets and non-immune cells and appear to regulate important aspects of innate and adaptive immune responses. Tubular epithelial cells are among the non-immune cells that express TLR1, -2, -3, -4, and -6, suggesting that these TLR might contribute to the activation of immune responses in tubulointerstitial injury (e.g., bacterial pyelonephritis, sepsis, and transplant nephropathy). In addition, TLR9 has been shown to be involved in antigen-induced immune complex glomerulonephritis and lupus nephritis by regulating humoral and cellular immune responses. TLR are evolutionary conserved regulators of innate and adaptive immune responses. It is likely that TLR are involved in many if not all types of renal inflammation. Here the authors provide an overview on the biology of TLR, summarize the present data on their expression in the kidney, and provide an outlook for the potential roles of TLR in kidney disease.
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PMID:Signaling danger: toll-like receptors and their potential roles in kidney disease. 1503 87

Urinary tract infection and pyelonephritis are mainly due to uropathogenic Escherichia coli (UPEC), and are common infectious diseases that constitute a significant cause of morbidity and mortality in humans. They are also the most frequent infectious complications in renal transplant patients, and can impair long-term renal graft function and outcome. UPEC may invade the kidneys via the systemic circulation or by local retrograde infection. They induce the proinflammatory mediators, which are intended to defend the host and clear bacteria from the kidneys. The Toll-like receptors (TLRs) play a key role in the recognition of bacterial components and in inducing the inflammatory response that is mediated by various intracellular signaling pathways. To date, 13 TLRs have been identified in mammals. Recent studies have provided evidence sug- Prof. Alain Vandewalle gesting that renal tubule epithelial cells express most of the TLRs initially identified in bone marrow-derived cells. Murine renal tubule cells express TLR1, 2, 3, 4, 6, and 11. TLR4, which recognizes lipopolysaccharide (LPS), the main constituent of Gram-negative bacteria, plays a key role in inducing the inflammatory responses elicited by UPEC. This review will consider some aspects of TLR function in the kidney, particularly in the renal tubule epithelial cells, and the role of these receptors in enabling the body to cope with urinary tract infections and pyelonephritis caused by UPECs.
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PMID:Toll-like receptors and renal bacterial infections. 1924 91