KSR1 Protects From Interleukin-10 Deficiency-Induced Colitis in Mice by Suppressing T-Lymphocyte Interferon-γ Production

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E−/−). STAT3E−/− mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E−/− mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor β. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon γ. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.

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Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4619 ◽

2020 ◽

Vol 8 (B) ◽

pp. 738-746

Author(s):

Haryudi Aji Cahyono ◽

Wisnu Barlianto ◽

Dian Handayani ◽

Handono Kalim

Keyword(s):

Vitamin D ◽

Type 1 Diabetes ◽

Transforming Growth Factor ◽

Interleukin 10 ◽

Interferon Γ ◽

Transforming Growth Factor Β1 ◽

Premature Atherosclerosis ◽

Ifn Γ ◽

Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

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Age-related aspects of cytokine profile of immune response in children with pertussis

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2020-65-3-84-90 ◽

2020 ◽

Vol 65 (3) ◽

pp. 84-90

Author(s):

O. P. Popova ◽

M. S. Blyakher ◽

I. M. Fedorova ◽

S. I. Koteleva ◽

I. V. Kapustin

Keyword(s):

Interleukin 2 ◽

Humoral Response ◽

Interleukin 10 ◽

Interferon Γ ◽

Interleukin 4 ◽

Cytokine Network ◽

Immunological Markers ◽

Age Related ◽

Immunoregulatory Cytokines ◽

The Relationship

The article presents a comparative analysis of the cytokine network in 161 patients with pertussis under the age of 1 year and in 180 patients over the age of 1 year. The studies revealed lower production of immunoregulatory cytokines (interferon-γ and interleukin-2) in patients under the age of 1 year at all stages of the disease and with all variants of pertussis (both mono- and mixed infections). The researchers revealed the relationship between the level of interferon-γ production and the severity of pertussis. They revealed age differences in the interferon-8 production in patients with mixed infection, which can determine clinical features and cause bronchopulmonary complications. The authors demonstrated the features of the dynamics of spontaneous and induced production of interleukin-6 and anti-inflammatory cytokines (interleukin-4, interleukin-10) in children under the age of 1 year; these features can be considered as immunological markers determining the imperfection of the humoral response in patients with pertussis in this age group.

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Synthetic Nano-selenium Improving Macrophage Immune Responses Treatment of Bladder Tumor Antigens

Immunoregulation ◽

10.32598/immunoregulation.4.1.3 ◽

2021 ◽

Vol 4 (1) ◽

pp. 43-52

Author(s):

Zeinab Agharezaie ◽

◽

Setareh Haghighat ◽

Mohammad Hossein Yazdi ◽

◽

...

Keyword(s):

Bladder Tumor ◽

Tumor Antigens ◽

Mrna Level ◽

Interleukin 10 ◽

Interferon Γ ◽

Selenium Nanoparticles ◽

Maximum Effect ◽

Mrna Levels ◽

Dependent Manner ◽

Tumor Lysate

Background: Synthetic nanoparticles are deemed to improve treatment with the least adverse effects. The effect of Selenium Nanoparticles (SeNPs) was reviewed on various pathogenic disorders. In the present project, the role of SeNPs on macrophage responses was assessed. Materials and Methods: SeNPs were prepared synthetically by ascorbic acid. Macrophages (MQs) were cultured and treated with SeNPs in combination with bladder tumor lysate and Bacillus Calmette Guerin (BCG). Other experimental groups include SeNPs + tumor lysate + MQs, BCG, BCG+MQs, and MQs. The mRNA levels of interferon-γ and interleukin-10 were evaluated using the real-time PCR method. Results: Synthetic selenium nanoparticles combined with the tumor lysate upregulated the mRNA level of interferon-γ after 12 and 24 h treatment. Regarding interleukin-10 expression, there were no remarkable differences in all experimental groups. The maximum effect of synthetic SeNPs was observed after 24 h treatment. Conclusion: The optimum effect of synthetic SeNPs presents in a treatment-dependent manner.

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