Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population

Chen, Yang-Fan; Xu, Jianhua; Zou, Yanfeng; Li, Lian; Wang, Fen; Chen, Shanyu; Cai, Jing

doi:10.1111/1756-185x.13191

Cited by 2 publications

(1 citation statement)

References 31 publications

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“…This latter phenomenon makes sense in light of SLE patients that experience glucocorticoid receptor desensitization as a result of exogenous glucocorticoid therapy. Additionally, glucocorticoid receptor polymorphisms have also been associated with SLE in certain populations, which suggests that glucocorticoid receptor desensitization could be a feature of SLE [ 45 , 46 ]. As in SLE patients, endogenous mechanisms of resistance to glucocorticoids operate in SLE mice and the augmented production of endogenous corticosterone in response to LPS is a compensatory, though ineffective, attempt [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

Pham

Mathis

2018

Brain Sciences

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Crosstalk between the brain and innate immune system may be dysregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease that presents with dysautonomia and aberrant inflammation. The hypothalamic-pituitary-adrenal (HPA) axis is an endogenous neuro-endocrine-immune pathway that can regulate inflammation following activation of vagal afferents. We hypothesized that chronic inflammatory processes in SLE are in part due to HPA axis dysfunction, at the level of either the afferent vagal-paraventricular nuclei (PVN) interface, the anterior pituitary, and/or at the adrenal glands. To study this, we challenged female control and SLE mice with lipopolysaccharide (LPS) and measured c-Fos expression as an index of neuronal activation, plasma adrenocorticotrophic hormone (ACTH) as an index of anterior pituitary function, and plasma corticosterone as an index of adrenal function. We found that c-Fos expression in the PVN, and plasma ACTH and corticosterone were comparable between unchallenged SLE and control mice. PVN c-Fos was increased similarly in control and SLE mice three hours after LPS challenge; however, there were no changes in plasma ACTH amongst any experimental groups post inflammatory challenge. Plasma corticosterone was markedly increased in LPS-challenged SLE mice compared to their vehicle-treated counterparts, but not in controls. Paradoxically, following LPS challenge, brain and spleen TNF-α were elevated in LPS-challenged SLE mice despite heightened plasma corticosterone. This suggests that, despite normal c-Fos expression in the PVN and activation of the HPA axis following LPS challenge, this cumulative response may not adequately defend SLE mice against inflammatory stimuli, leading to abnormally heightened innate immune responses and peripheral inflammation.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

Pham

Mathis

2018

Brain Sciences

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The clinical significance of the glucocorticoid receptors: Genetics and epigenetics

Motavalli

Majidi

Pourlak

et al. 2021

The Journal of Steroid Biochemistry and Molecular Biology

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Association of glucocorticoid receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population

Abstract: The study indicates that GR genetic polymorphisms may play a major role in the pathogenesis and development of SLE.

Cited by 2 publications

References 31 publications

Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

Lipopolysaccharide Challenge Reveals Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Murine Systemic Lupus Erythematosus

The clinical significance of the glucocorticoid receptors: Genetics and epigenetics

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