Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophages from older men and postmenopausal women

Abstract

Inflammation plays a central role in the development and progression of coronary heart disease (CHD). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophages obtained from younger individuals. The effect of these hormones on the expression of proinflammatory markers in macrophages obtained from a CHD age-relevant population has not been studied. Human monocyte-derived macrophages (HMDMs) were obtained from healthy normolipidemic men and postmenopausal women (age 50-70 years), and cultured in autologous serum along with both physiological and supraphysiological concentrations of estrogen or testosterone. HMDMs were stimulated with oxidized low-density lipoproteins, and the expression of the cytokines tumor necrosis factor a (TNF-a or TNF), interleukin (IL)6, and IL-1b (IL1B) and of the acute-phase protein C-reactive protein (CRP) was measured. Both physiological and supraphysiological concentrations of testosterone reduced the expression and secretion of TNF-a and reduced the expression of IL-1b, but did not affect the expression of IL6 or CRP. Estrogen did not modify the expression of TNF-a, IL6, and IL-1b. Estrogen caused a variable response in CRP expression that was positively associated with the plasma small dense LDL-cholesterol concentration of the donors. There were no gender differences in any of the observed effects. Our results indicate that testosterone may exert anti-inflammatory effects by reducing macrophage TNF-a expression, while the effects of estrogen on macrophage CRP expression may depend upon the extracellular lipid environment.

The differences of sarcopenia-related phenotypes: effects of gender and population

“…In fact, numerous previous studies have constantly reported that TC is significantly positively associated with IS in vivo [24,38,40,46,54], and both of them can be improved with MMIs, muscle mass indexes, were expressed as mean ± SD exercise [3,5,11,20,36,37,42,48]. The increased plasma TC in male rats during exercise is at least partially a result of lactate's effect on the secretion of testosterone [30,31], and testosterone may suppress the expression of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 [8,32]. In experimental models, these proinflammatory cytokines disrupt normal insulin action in fat and muscle cells, and this may be the major factor in causing the whole body IR observed in patients with visceral adiposity [47].…”

Testosterone: a vascular hormone in health and disease

“…5). The physiological and supraphysiological concentrations of testosterone reduced the expression and secretion of TNFa and IL1b in monocyte-derived macrophages obtained from a CHD age-relevant population, although no effects were observed on IL6 and CRP expression (Corcoran et al 2010). In another study, IL6 production was shown to be reduced in isolated human monocytes from a small healthy male population following in vitro testosterone treatment (Kanda et al 1996).…”

Small Dense LDL Enhances THP-1 Macrophage Foam Cell Formation

“…Another reason may be that native sd-LDL has distinct properties to induce lipid accumulation in macrophages. It has recently been reported that estrogen-induced C reactive protein gene expression in human monocytederived macrophages was correlated with sd-LDL cholesterol levels, but not LDL cholesterol levels in the plasma used for incubation 19) . To investigate whether scavenger receptors might relate to the increase of lipid accumulation, we measured the expression (both mRNA and protein) of SR-A, CD36 and LOX-1 by macrophages.…”