Testosterone inhibits tumor necrosis factor‐α‐induced vascular cell adhesion molecule‐1 expression in human aortic endothelial cells

Hatakeyama, Hyōe; Nishizawa, Makoto; Nakagawa, Atsushi; Nakano, Shigeru; Kigoshi, Toshikazu; Uchida, Kenzo

doi:10.1016/s0014-5793(02)03440-3

Cited by 97 publications

(65 citation statements)

References 30 publications

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“…We demonstrate that DHT inhibits NF-kB activation, a master transcription factor in inflammation, as evidenced by its reduced nuclear translocation and by the decreased expression of COX2. A similar antiinflammatory effect has been described also in human endothelial cells, where DHT or testosterone decreased TNFa-induced inflammatory response through the inhibition of NF-kB signaling pathway (Hatakeyama et al 2002, Norata et al 2006.…”

Section: Discussionsupporting

confidence: 72%

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Vignozzi

Cellai²,

Santi³

et al. 2012

Journal of Endocrinology

127

107

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Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor a, lipopolysaccharide, or CD4 C T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4 C T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon g inducible protein 10, IP10), and Th2 (IL9)-and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-kB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

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Section: Discussionsupporting

confidence: 72%

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Vignozzi

Cellai²,

Santi³

et al. 2012

Journal of Endocrinology

127

107

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“…TNFa-induced VCAM-1 expression in HAECs was inhibited by testosterone treatment, suggesting that androgens play an important role in the prevention of atherogenesis (Hatakeyama et al 2002). This study additionally described the inhibition of nuclear factor kB (NFkB) activation, not only as a potential mechanism for decreased VCAM-1 expression, but also as a prospective modulator of several other inflammatory gene targets known to be activated by this transcription factor.…”

Section: Influence Of Testosterone On Vascular Cell Inflammationmentioning

confidence: 73%

“…Research suggests that the expression of VCAM-1, as induced by pro-inflammatory cytokines such as TNFa or interferon g (IFNg (IFNG)) in endothelial cells, can be attenuated by treatment with testosterone (Hatakeyama et al 2002, Mukherjee et al 2002. Testosterone also inhibits the production of pro-inflammatory cytokines such as IL6, IL1b and TNFa in a range of cell types including human endothelial cells (Hatakeyama et al 2002).…”

Section: Influence Of Testosterone On Vascular Cell Inflammationmentioning

confidence: 99%

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Testosterone: a vascular hormone in health and disease

Kelly¹,

Jones²

2013

Journal of Endocrinology

239

177

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Coronary heart disease is a leading cause of premature death in men. Epidemiological studies have shown a high prevalence of low serum testosterone levels in men with cardiovascular disease (CVD). Furthermore, a low testosterone level is associated in some but not in all observational studies with an increase in cardiovascular events and mortality. Testosterone has beneficial effects on several cardiovascular risk factors, which include cholesterol, endothelial dysfunction and inflammation: key mediators of atherosclerosis. A bidirectional relationship between low endogenous testosterone levels and concurrent illness complicates attempts to validate causality in this association and potential mechanistic actions are complex. Testosterone is a vasoactive hormone that predominantly has vasodilatory actions on several vascular beds, although some studies have reported conflicting effects. In clinical studies, acute and chronic testosterone administration increases coronary artery diameter and flow, improves cardiac ischaemia and symptoms in men with chronic stable angina and reduces peripheral vascular resistance in chronic heart failure. Although the mechanism of the action of testosterone on vascular tone in vivo is not understood, laboratory research has found that testosterone is an L-calcium channel blocker and induces potassium channel activation in vascular smooth muscle cells. Animal studies have consistently demonstrated that testosterone is atheroprotective, whereas testosterone deficiency promotes the early stages of atherogenesis. The translational effects of testosterone between in vitro animal and human studies, some of which have conflicting effects, will be discussed in this review. We review the evidence for a role of testosterone in vascular health, its therapeutic potential and safety in hypogonadal men with CVD, and some of the possible underlying mechanisms.

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“…Several studies have revealed that androgens enhance tumor necrosis factor and vascular cell adhesion molecule-1 expressions through interaction between the AR and nuclear factor-kappa B signaling pathway [66][67][68] . Androgens also inhibit the production of interleukin 6, interleukin 1 beta, and expression of the intracellular adhesion molecule-1 and monocyte chemoattractant protein-1 in various cell types 69,70) . We previously demonstrated that the AR provides protective effects against angiotensin II-induced vascular remodeling by regulating oxidative stress, c-Jun N-terminal kinase signaling, and transforming growth factor phosphorylated-Smad pathway using AR knockout mice 27) .…”

Section: Ar Plays a Pivotal Role In Vegf-stimulated Akt And Enos Signmentioning

confidence: 99%

Roles of the Androgen – Androgen Receptor System in Vascular Angiogenesis

Yoshida

Ikeda

Aihara

2016

JAT

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Although many clinical studies have shown that a low testosterone level is associated with cardiovascular diseases, the role of androgens in cardiovascular physiology and pathophysiology remains controversial. Androgens exert various actions in their target organs, and the androgen receptor (AR) is widely distributed in several tissues, including endothelial cells, smooth muscle cells, and fibroblasts, in the vascular system. Biological activities of androgens are predominantly mediated through the AR by the transcriptional control of target genes and interaction with multiple signaling pathways. To clarify the molecular mechanisms of androgens in cardiovascular disease, we examined a pathological model using AR knockout mice and showed that the androgen -AR system has protective effects on cardiovascular remodeling against cardiovascular stress. In this review, we focus on the role of the androgen -AR system in angiogenesis after ischemic stress.

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Testosterone inhibits tumor necrosis factor‐α‐induced vascular cell adhesion molecule‐1 expression in human aortic endothelial cells

Cited by 97 publications

References 30 publications

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Testosterone: a vascular hormone in health and disease

Roles of the Androgen – Androgen Receptor System in Vascular Angiogenesis

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