IL-1β promotes tubulointerstitial injury in MPO-ANCA-associated glomerulonephritis
| Autor: | Naoko Ueki, Satoshi Hisano, Aki Hamauchi, Katsuhisa Miyake, Maho Watanabe, Yasuhiro Abe, Renya Watanabe, Ritsuya Noda, Manabu Tashiro, Kenji Ito, Tetsuhiko Yasuno, Hitoshi Nakashima, Yoshie Sasatomi |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Inflammasomes Interleukin-1beta Kidney Glomerulus Inflammation Antibodies Antineutrophil Cytoplasmic 03 medical and health sciences Glomerulonephritis Humans Medicine Aged Retrospective Studies Kidney Reverse Transcriptase Polymerase Chain Reaction business.industry Macrophages Interleukin Inflammasome General Medicine Neutrophil extracellular traps Middle Aged medicine.disease Immunohistochemistry Toll-Like Receptor 4 030104 developmental biology medicine.anatomical_structure Nephrology TLR4 Nephritis Interstitial Female medicine.symptom business Nephritis medicine.drug |
| Zdroj: | Clinical Nephrology. 86:190-199 |
| ISSN: | 0301-0430 |
| DOI: | 10.5414/cn108902 |
| Popis: | Background It is widely accepted that tubulointerstitial injury (TII) is caused by glomerular injury (GI) in glomerular diseases. Glomerular endocapillary inflammation may result in crescent formation and exuded protein leakage, which may induce TII in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCAGN). However, some reports have indicated a glomerulonephritis-independent mechanism of TII in ANCAGN. The aim of this study was to determine the principle cytokines correlated with TII severity and to elucidate a characteristic mechanism for TII in ANCAGN. Methods 28 myeloperoxidase-ANCA-positive ANCAGN patients were enrolled, and their kidney biopsy specimens were histologically evaluated with regard to GI and TII. The mRNA expression of various cytokines was examined in 28 specimens. Results Interleukin (IL)-1β was significantly correlated with the severity of TII. The mRNA expression of Toll-like receptor 4 (TLR4) and Nod-like receptor family pyrin domain-containing-3 (NLRP3) also correlated with TII severity. Immunohistochemical analysis demonstrated that TLR4 protein was positively stained in the tubulointerstitial infiltrating cells. NRLP3 protein was detected in macrophages in the severe infiltrating area but was absent or only very faintly expressed in the glomeruli. These results indicated that NLRP3 inflammasome-dependent processing in macrophages releases the mature active form of IL-1β, which may lead to the development and deterioration of TII. Conclusions Sterile inflammation leads to the formation of ANCA-mediated neutrophil extracellular traps (NETs), which may stimulate macrophages and dendritic cells via TLR4 and induce NF-κB-dependent mRNA expression and translation of pro-IL-1β. Simultaneously, damage-associated molecular pattern signals resulting from NETs promote NLRP3 inflammasome-dependent processing and release mature active IL-1β. Sterile inflammation utilizing the NLRP3 inflammasome might be a characteristic reaction limited to the tubulointerstitium. Thus, neutralizing IL-1β may be a promising strategy to suspend the progress of TII and improve the prognosis of chronic kidney disease resulting from ANCAGN. . |
| Databáze: | OpenAIRE |
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