title: Circulating nucleic acids as possible damage-associated molecular patterns in different stages of renal failure.
abstract: Chronic renal failure (CRF) is a condition associated with the risk of cardiovascular complications. Systemic inflammatory response, initiated by the pathogen-associated molecular-pattern (PAMP) molecules, exerts many similarities with the damage-associated molecular-pattern (DAMP) molecule-induced systemic response. Up to now, a number of DAMP molecules were identified. We hypothesized that the available circulating nucleic acids, acting as DAMPs, may modulate immunoinflammatory reaction in CRF. Patients with the different stages of chronic kidney disease, kidney transplantation, and patients on dialysis were included in the study. Obtained results about higher concentration of circulating ribonucleic acid (RNA), according to the stages of kidney diseases, may contribute to the hypothesis that damaged kidney tissue releases nucleic acids. Circulating RNAs expressed maximal absorbance peak at 270 nm in spectrophotometric scan analysis, which corresponded to polyC, compared to different standard samples. During in vitro conditions, by using the culture of human residential macrophages, circulating RNA isolated from patients with IV-V-stage renal diseases, patients on hemodialysis, and patients who underwent renal transplantation were able to significantly change signal transduction proteins related to inflammation and antiviral response. They significantly increased the intracellular concentration of active nuclear transcription factor nuclear factor kappa B (NF-kappaB), interferon regulatory factors (IRF)-3, and IRF-7 and significantly decreased melanoma differentiation-associated protein-5 (MDA-5) and p38. In this way, it seems that circulating RNA, acting as DAMP, may contribute to the mechanisms of additional inflammatory reaction, possible immune destruction, and decreased antiviral response, related to complications in kidney diseases.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Nis, 18000 Nis, Serbia. kocicrg@yahoo.co.uk
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocić
authors.forename: Sonja
authors.initials: S
authors.lastname: Radenkovic
authors.forename: Tatjana
authors.initials: T
authors.lastname: Cvetkovic
authors.forename: Avrelija
authors.initials: A
authors.lastname: Cencic
authors.forename: Francesco
authors.initials: F
authors.lastname: Carluccio
authors.forename: Dijana
authors.initials: D
authors.lastname: Musovic
authors.forename: Goran
authors.initials: G
authors.lastname: Nikolić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Jevtović-Stoimenov
authors.forename: Dusan
authors.initials: D
authors.lastname: Sokolović
authors.forename: Boban
authors.initials: B
authors.lastname: Milojkovic
authors.forename: Jelena
authors.initials: J
authors.lastname: Basic
authors.forename: Andrej
authors.initials: A
authors.lastname: Veljkovic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Stojanović
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D018929:Cell Culture Techniques; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology; D008262:Macrophage Activation; D009696:Nucleic Acids / Q000097:blood* / Q000276:immunology; D012313:RNA / Q000097:blood / Q000276:immunology; D006435:Renal Dialysis
chemical_list: D015415:Biomarkers; D016207:Cytokines; D009696:Nucleic Acids; D012313:RNA