Interleukin‐6 increases adrenal androgen release by regulating the expression of steroidogenic proteins in NCI‐H295R cells

Xian, Wa; Zhang, Junfeng; Peng, Wei; Xu, Hao; Wei, Zhewen; Pang, Linhao; Liu, Jihong; Wang, Tao

doi:10.1002/jcp.29748

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Providing evidence of a role for altered cytokine levels in the observed normalisation of corticosterone fluctuations in SGLT2 null mice, treatment of adrenal gland cells with IL-6 upregulated CYP11A1 and HSD3B2, in line with previous findings (39). An upward trend was also observed following treatment with leptin (40) and IL-1β (41), while IL-10 and TGFβ1 had no effect, again mirroring earlier results (42,43).…”

Section: Discussionsupporting

confidence: 87%

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels

Brisnovali,

Franco,

Abdelgawwad

et al. 2024

Preprint

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Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing Type 2 Diabetes (T2D). Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urinary glucose excretion. However, the full scope of their mechanisms extends beyond glycaemic control. At present, their immunometabolic effects remain elusive. To investigate the effects of SGLT2 inhibition or deletion, we compared the metabolic and immune phenotype between high fat diet-fed control, chronically dapagliflozin-treated mice and total-body SGLT2/Slc5a2 knockout mice. SGLT2 null mice exhibited superior glucose tolerance and insulin sensitivity compared to control or dapagliflozin-treated mice, independent of glycosuria and body weight. Moreover, SGLT2 null mice demonstrated physiological regulation of corticosterone secretion, with lowered morning levels compared to control mice. Systemic cytokine profiling also unveiled significant alterations in inflammatory mediators, particularly interleukin 6 (IL-6). Furthermore, unbiased proteomic analysis demonstrated downregulation of acute-phase proteins and upregulation of glutathione-related proteins, suggesting a role in the modulation of antioxidant responses. Conversely, IL-6 increased SGLT2 expression in kidney HK2 cells suggesting a role for cytokines in the effects of hyperglycemia. Collectively, our study elucidates a potential interplay between SGLT2 activity, immune modulation, and metabolic homeostasis.

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Section: Discussionsupporting

confidence: 87%

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels

Brisnovali,

Franco,

Abdelgawwad

et al. 2024

Preprint

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“…Furthermore, LH and DHEAS hormone levels were significantly correlated with IL-6 levels. Interestingly DHEAS and IL-6 have a correlation in healthy women but not in PCOS women (24). Additionally, ANOVA and following Bonferroni multiple comparisons showed that DHEAS level had significant changes between groups and among subjects in PCOS women and control women.…”

Section: Discussionmentioning

confidence: 85%

Elevated Serum Level of DHEAS as a Hormone and IL-6 as a Proinflammatory Cytokine May Better Indicate Metabolic Syndrome in PCOS Women

2021

JMPB

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Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women, indeed multifactorial condition. Cytokines such as TNF-alpha and IL-6 have influence on several metabolic activities. The increase in dehydroepiandrosterone (DHEA) is thought to play an important role in IL-6-mediated pathogenetic effects in PCOS women. The aim of this study is to explore whether TNF-alpha and IL-6 are correlated hormone levels in PCOS disease. We recruited 65 PCOS patients and 45 healthy controls. The serum IL-6, TNF-alpha, levels were measured by ELISA and clinical characteristics were measured. Both serum IL-6, TNF-alpha levels (p<0.01), or the serum TSH, FSH, LH, PRL levels were significantly higher in the patients of PCOS (p<0.01). Serum IL-6 levels were correlated with DHEAS level (r=-0.4186, p<0.01). DHEAS level tended to be higher in PCOS women with a correlation between age, BMI, IL-6 level and positively correlated with FSH, LH and PRL levels (p<0.01). There was an elevation of TSH level in the PCOS group (2.4±1.5) vs. control group (1.8±1.6). However, in control samples, there was no correlation between TNF alpha and IL-6, while in the PCOS samples positive correlation, was obtained. Oral glucose tolerance test (OGTT) was higher than the control (20.38±13.2) group vs. PCOS women (128.33±33.8) but only 3.44 % of them had Type II diabetes. HOMA-IR index was higher in the PCOS group (8.26±15.06) vs. control group (2.12±0.88) too. There was a correlation between age and IL-6 level and BMI. Serum IL-6 and DHEAS levels were significantly altered in PCOS patients and determined which might be PCOS prognostic importance.

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“…Nagy intenzitású és hosszú időtartamú edzés hatására a limfociták száma csökken, míg a neutrofilek koncentrációja nő, például az adrenalin és CTOL hatására [101]. De a glükokortikoid vonalon túl elősegítheti az androgének szekrécióját az olyan gének expressziójának szabályozásával, amelyek az androgének szintetikus útvonalához kötöttek [102]. Az IL-6 mellett a szintén citokinek közé tartozó tumor nekrózis faktor-alfa (TNF-α) is jelen van az emberi mellékvesekéregben is.…”

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Az extrém fizikális és mentális terhelés, valamint az endogén szteroid bioszintézis összefüggései professzionális sportolóknál

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Az élsportolók az edzések, illetve mérkőzések során folyamatos intenzív mentális és fizikai megterhelésnek vannak kitéve. A stressz hatására a hipotalamusz–hipofízis–mellékvese tengely, valamint a hipotalamusz-hipofízis-gonád tengely aktiválódik, így a mellékvesekéregben, gonádokban, perifériákon fokozódik a szteroid hormontermelés. Kutatásunk során célunk volt élsportolók endogén szteroid-profilját vizsgálni extrém fizikai, valamint extrém mentális terhelés hatására. A terhelések során vérvétel történt a terhelés előtt nyugalmi állapotban, a terhelés maximumán, valamint 30 perccel a terhelést követően. A vizsgálati mintákból folyadékkromatográffal kapcsolt tandem tömegspektrométerrel szteroid-profil meghatározást végeztünk, egyidejűleg 16 endogén szteroid hormon koncentrációját határoztuk meg. Akut extrém fizikai terhelés hatására minden vizsgált szteroid hormon legalább egy terhelési fázisában szignifikáns növekedést mutatott. Szelektív aktiválódást extrém fizikai terhelés hatására sem a mellékvesekéreg zónái, sem a szteroid hormonokat termelő szervek nem mutattak. Az élsportolók endogén szteroid hormon szintjeinek legjelentősebb változását extrém akut fizikai terhelésnél a restitúciós fázisban azonosítottuk. Az alkalmazott módszertan alkalmas volt élsportolók endokrin homeosztázisának monitorozására, a terhelésre adott válasz jellemzésére.

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Interleukin‐6 increases adrenal androgen release by regulating the expression of steroidogenic proteins in NCI‐H295R cells

Cited by 4 publications

References 33 publications

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels

Effects of SGLT2 Ablation or Inhibition on Corticosterone Secretion in High-Fat-Fed Mice: Exploring a Nexus with Cytokine Levels

Elevated Serum Level of DHEAS as a Hormone and IL-6 as a Proinflammatory Cytokine May Better Indicate Metabolic Syndrome in PCOS Women

Az extrém fizikális és mentális terhelés, valamint az endogén szteroid bioszintézis összefüggései professzionális sportolóknál

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