An Essential Role for NF-κB in IL-18-Induced IFN-γ Expression in KG-1 Cells

Kojima, Hiroyuki; Aizawa, Yasushi; Yanai, Yoshiaki; Nagaoka, Katsue; Takeuchi, Makoto; Ohta, Toshio; Ikegami, Hiromasa; Ikeda, Masao; Kurimoto, Masashi

doi:10.4049/jimmunol.162.9.5063

Cited by 89 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Nrlp3 inflammasome, which increases mature IL-18, aggravates DN (46). IL-18 is a prominent inducer of IFN- γ via NF- κ B (47, 48), and NF- κ B inhibition attenuates diabetic kidney injury (49). IFN- γ is upregulated in patients with diabetes and kidney disease compared with diabetes alone (50), and IFN- γ also upregulates the inflammasome (51).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

et al. 2022

View full text Add to dashboard Cite

BackgroundDiabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored.MethodsUsing hydrodynamic tail-vein injection, we overexpress Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli.ResultsIn DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that overexpression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury, independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease–promoting and interferon (IFN)-related genes, includingAckr2andCxcl11.ConclusionsWe demonstrate that, in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select IFN signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…IL‐18 acts through NF‐κB for the modulation of many of the inflammatory responses (Akira, ; Kojima et al, ). IL‐18 induces T‐lymphocyte activity via NF‐κB pathway (Weinstock, Blum, Metwali, Elliott, & Arsenescu, ), it can induce IL‐1, TNF‐α, and IL‐6 expression by NF‐κB dependent pathway (Kojima et al, ; Liu, Zhang, Joo, & Sun, ); therefore, many aspects of IL‐18 inflammation are mediated through NF‐κB signaling pathways (Donate‐Correa, Martín‐Núñez, Muros‐de‐Fuentes, Mora‐Fernández, & Navarro‐González, ; Kojima et al, ; Matsumoto et al, ).…”

Section: Pathogenic Roles Of Il‐18 In the Onset And Progression Of Dn...mentioning

confidence: 99%

Interleukin‐18 and diabetic nephropathy: A review

Yaribeygi

Atkin

Sahebkar

2018

Journal Cellular Physiology

View full text Add to dashboard Cite

The inflammatory response has an important role in the pathophysiology of diabetic nephropathy that is contributed to by inflammatory mediators such as interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-α, and macrophage chemotactic protein-1; however, the role of IL-18 seems to be more specific than other cytokines in the inflammatory process. IL-18 is expressed in renal tissue and is upregulated by several stimuli including hyperglycemia. The expression/urinary level of IL-18 is positively correlated with the progression of diabetic nephropathy and the urinary albumin excretion rate. In this review, we have focused on the molecular pathways modulating the relationship between IL-18 and diabetic nephropathy.apoptosis, diabetic nephropathy, inflammatory response, interleukin-18, oxidative stress, tumor necrosis factor-α

show abstract

“…Further, western blot analysis of exosomes prepared from the cell-free supernatant of HeLa cells showed an association of IL-18 with the exosomes ( Figure 6B ). IL-18 was reported to modulate IFN-γ expression via NF-κB and MAPK kinase mediated pathways [ 35 ]. Therefore, the role of NF-κB and MAPK molecules in the modulation of IFN-γ were further investigated.…”

Section: Resultsmentioning

confidence: 99%

Acidic environment could modulate the interferon-γ expression: Implication on modulation of cancer and immune cells’ interactions

Sharma,

Kaur

2023

Asian Biomedicine

View full text Add to dashboard Cite

Background In rapidly growing solid tumors, insufficient vascularization and poor oxygen supply result in an acidic tumor microenvironment, which can alter immune response. Objective To investigate the role of the acidic microenvironment in immune response modulation along with cancer and immune cells’ interactions. Method To mimic the tumor microenvironment conditions, T cells (Jurkat), macrophages (THP-1), and HeLa (cervical) cells were cultured under acidic conditions (pH 6.9, pH 6.5) and physiological pH (7.4). The HeLa cell culture medium was exploited as a tumor cell conditioned medium. Real-time PCR was carried out to quantify the mRNA levels, while flow cytometry and western blot hybridization was carried out to ascertain the levels of different proteins. Results The acidic microenvironment around the T cells (Jurkat) and macrophage cells (THP-1) could lead to the downregulation of the interferon gamma (IFN-γ). An increase in IFN-γ expression was observed when Jurkat and macrophage cells were cultured in HeLa cells conditioned medium (HCM) at low pH (pH 6.9, pH 6.5). The HeLa cells under acidic environment (pH 6.9, pH 6.5) upregulated interleukin 18 levels and secreted it as exosome anchored. Additionally, enhanced nuclear localization of NF-κB was observed in Jurkat and THP-1 cells cultured in HCM (pH 6.9, pH 6.5). Jurkat and THP-1 cultured in HCM revealed enhanced cytotoxicity against the HeLa cells upon reverting the pH of the medium from acidic to physiological pH (pH 7.4). Conclusion Collectively, these results suggest that the acidic microenvironment acted as a key barrier to cancer and immune cells’ interactions.

show abstract

An Essential Role for NF-κB in IL-18-Induced IFN-γ Expression in KG-1 Cells

Cited by 89 publications

References 49 publications

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

Interleukin‐18 and diabetic nephropathy: A review

Acidic environment could modulate the interferon-γ expression: Implication on modulation of cancer and immune cells’ interactions

Contact Info

Product

Resources

About