Autor: Ribeiro, Andrea - Prolib Integro

Skocz do pozycji: 1.

Tytuł:: Macrophage-specific MCPIP1/Regnase-1 attenuates kidney ischemia-reperfusion injury by shaping the local inflammatory response and tissue regeneration
Autorzy:: Ribeiro, Andrea
Wadowska, Marta
Köhler, Paulina
Schmaderer, Christoph
Krill, Moritz
Steiger, Stefanie
Dobosz, Ewelina
Kozieł, Joanna
Lech, Maciej
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 2.

Tytuł:: Bidirectional interaction between chronic kidney disease and Porphyromonas gingivalis infection drives inflammation and immune dysfunction
Autorzy:: Anders, Hans-Joachim
Potempa, Jan
Wadowska, Marta
Schmaderer, Christoph
Adamowicz, Karina
Golda, Anna
Lima Ribeiro, Andrea Sofia
Kozieł, Joanna
Lech, Maciej
Opis:: Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system’s response to infections. Our research investigates the progression of Porphyromonas gingivalis (P. gingivalis) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short-term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen-associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis. In vivo, CKD significantly enhanced P. gingivalis survival and infection-induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis-infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 3.

Tytuł:: Murine myeloid cell MCPIP1 suppresses autoimmunity by regulating B-cell expansion and differentiation
Autorzy:: Dobosz, Ewelina
Fu, Mingui
Potempa, Jan
Lorenz, Georg
Wadowska, Marta
Kozieł, Joanna
Lech, Maciej
Schmaderer, Christoph
Würf, Vivian
Kotlinowski, Jerzy
Ribeiro, Andrea
Opis:: Myeloid-derived cells, in particular macrophages, are increasingly recognized as critical regulators of the balance of immunity and tolerance. However, whether they initiate autoimmune disease or perpetuate disease progression in terms of epiphenomena remains undefined. Here, we show that depletion of MCPIP1 in macrophages and granulocytes ($Mcpip1^{fl/fl}-LysM^{cre+}$ C57BL/6 mice) is sufficient to trigger severe autoimmune disease. This was evidenced by the expansion of B cells and plasma cells and spontaneous production of autoantibodies, including anti-dsDNA, anti-Smith and anti-histone antibodies. Consequently, we document evidence of severe skin inflammation, pneumonitis and histopathologic evidence of glomerular IgG deposits alongside mesangioproliferative nephritis in 6-month-old mice. These phenomena are related to systemic autoinflammation, which secondarily induces a set of cytokines such as Baff, Il5, Il9 and Cd40L, affecting adaptive immune responses. Therefore, abnormal macrophage activation is a key factor involved in the loss of immune tolerance. Overall, we demonstrate that deficiency of MCPIP1 solely in myeloid cells triggers systemic lupus-like autoimmunity and that the control of myeloid cell activation is a crucial checkpoint in the development of systemic autoimmunity.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 4.

Tytuł:: Uremic toxin indoxyl sulfate promotes macrophage-associated low-grade inflammation and epithelial cell senescence
Autorzy:: Ribeiro, Andrea
Anders, Hans-Joachim
Wadowska, Marta
Srebrzynski, Matthias
Schmaderer, Christoph
Rother, Simone
Adamowicz, Karina
Steiger, Stefanie
Liu, Feiyue
Kozieł, Joanna
Lech, Maciej
Opis:: In this study, we investigated the impact of the uremic toxin indoxyl sulfate on macrophages and tubular epithelial cells and its role in modulating the response to lipopolysaccharide (LPS). Indoxyl sulfate accumulates in the blood of patients with chronic kidney disease (CKD) and is a predictor of overall and cardiovascular morbidity/mortality. To simulate the uremic condition, primary macrophages and tubular epithelial cells were incubated with indoxyl sulfate at low concentrations as well as concentrations found in uremic patients, both alone and upon LPS challenge. The results showed that indoxyl sulfate alone induced the release of reactive oxygen species and low-grade inflammation in macrophages. Moreover, combined with LPS (proinflammatory conditions), indoxyl sulfate significantly increased TNF-α, CCL2, and IL-10 release but did not significantly affect the polarization of macrophages. Pre-treatment with indoxyl sulfate following LPS challenge induced the expression of aryl hydrocarbon receptor (Ahr) and NADPH oxidase 4 (Nox4) which generate reactive oxygen species (ROS). Further, experiments with tubular epithelial cells revealed that indoxyl sulfate might induce senescence in parenchymal cells and therefore participate in the progression of inflammaging. In conclusion, this study provides evidence that indoxyl sulfate provokes low-grade inflammation, modulates macrophage function, and enhances the inflammatory response associated with LPS. Finally, indoxyl sulfate signaling contributes to the senescence of tubular epithelial cells during injury.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego

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Skocz do pozycji: 5.

Tytuł:: GDF-15 suppresses puromycin aminonucleoside-induced podocyte injury by reducing endoplasmic reticulum stress and glomerular inflammation
Autorzy:: Ribeiro, Andrea
Honarpisheh, Mohsen
Anders, Hans-Joachim
Klaus, Martin
Köhler, Paulina
Schmaderer, Christoph
Adamowicz, Karina
Liu, Min
Li, Chenyu
von Rauchhaupt, Ekaterina
Lindenmeyer, Maja
Steiger, Stefanie
Lech, Maciej
Opis:: GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin–creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.
Dostawca treści:: Repozytorium Uniwersytetu Jagiellońskiego