التفاصيل البيبلوغرافية
| العنوان: |
Urinary Mitochondrial DNA Induces an Inflammatory Response in Peripheral Blood Mononuclear Cells. |
| المؤلفون: |
Yadav, Brijesh, Prasad, Narayan, Kushwaha, Ravi Shanker, Singh, Ankita, Yadav, Deependra, Bhadauria, Dharmendra Singh, Kaul, Anupma |
| المصدر: |
Indian Journal of Transplantation; Apr-Jun2024, Vol. 18 Issue 2, p132-137, 6p |
| مصطلحات موضوعية: |
KIDNEY transplantation, FLOW cytometry, MONONUCLEAR leukocytes, CELL physiology, ENZYME-linked immunosorbent assay, ACUTE kidney failure, REVERSE transcriptase polymerase chain reaction, TRANSCRIPTION factors, DESCRIPTIVE statistics, SURGICAL complications, CELL culture, MESSENGER RNA, GENE expression, ONE-way analysis of variance, INFLAMMATION, NATURAL immunity, CYTOKINES, DATA analysis software, MITOCHONDRIAL DNA, COVID-19, INTERLEUKINS, DISEASE risk factors |
| مستخلص: |
Background: Mitochondria are semiautonomous cell organelles having its own nucleic acid. Mitochondrial DNA (Mt‑DNA) remain in hypomethylated (CpG) state and impose an immunogenic response by binding to the toll‑like receptor (TLR‑9) through the NF‑kB pathway. Innate immune cells recognize the hypomethylated pattern of mt‑DNA and quickly trigger the innate immune response. The immunomodulatory effects of urinary mt‑DNA derived from renal transplant recipients with COVID‑19‑associated acute kidney injury (AKI) have not been studied. Materials and Methods: Healthy donor peripheral blood mononuclear cell (PBMC) was cultured with the urinary Mt‑DNA derived from the renal transplant recipients, who previously developed SARS‑CoV‑2 infection associated AKI. Cell activation was measured by the flow cytometry. In cell pellets, interleukin IL‑6, IL‑10, and Myd88, TLR‑9 mRNA transcript expression was measured by the reverse transcription polymerase chain reaction. The IL‑6 and IL‑10 cytokine levels were measured by the enzyme‑linked immunosorbent assay in culture supernatants. Results: The urinary mitochondrial DNA (umt‑DNA) significantly induces the activation of > 75% of PBMCs. The m‑RNA transcript expression of the inflammatory gene in control versus umt‑DNA treated PBMCs was for IL‑6 (0.99 ± 0.05 vs. 2.18 ± 1.15 au; P = 0.004), MYD88 was (1.00 ± 0.05 vs. 1.55 ± 0.31; P < 0.001), TLR‑9 (1.00 ± 0.05 vs. 3.33 ± 1.37 au; P < 0.001) was upregulated, and the IL‑10 (1.00 ± 0.13 vs. −1.73 ± 0.58; P < 0.001) level was downregulated. However, in PBMC culture supernatants, IL‑6 level in control versus umt‑DNA‑treated groups were (37.50 ± 13.79 vs. 186.9 ± 15.50 pg/mL; P < 0.001), which was significantly higher in umt‑DNA‑treated groups and the IL‑10 (8.80 ± 2.16 vs. 7.60 ± 3.12 pg/mL; P = 0.32) level was similar between the control‑ and umt‑DNA‑treated groups. Conclusions: Urinary Mt‑DNA significantly induces the inflammatory cytokine IL‑6 secretion from the PBMCs through the Myd88‑dependent pathway. [ABSTRACT FROM AUTHOR] |
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