Exercise reduced pentraxin 3 levels produced by endotoxin-stimulated human peripheral blood mononuclear cells in obese individuals

Abstract

Impact statementOur laboratory has previously demonstrated that obese individuals present with lower plasma concentrations of the antiinflammatory protein pentraxin 3 (PTX3), whereas acute aerobic exercise increases plasma PTX3 levels similarly compared to normal-weight individuals. As a follow-up, the present study demonstrates that PBMCs isolated from obese and normalweight individuals produce comparable amounts of PTX3 ex vivo in response to lipopolysaccharide (LPS). Furthermore, given that acute aerobic exercise reduced the ex vivo production of PTX3 in both groups, our results clearly indicate that plasma PTX3 levels are relatively independent of those produced by PBMCs ex vivo. In addition, our findings suggest that the mechanisms associated with PTX3-mediated production of the anti-inflammatory cytokine interleukin 10 may be impaired in obese individuals, and thus provides a key finding necessary for the elucidation of PTX3's role in the mediation of anti-inflammatory profiles and the subsequent amelioration of inflammatory disease during obesity. AbstractThe purpose of this study was to determine whether obesity would reduce the capacity of peripheral blood mononuclear cells (PBMCs) to produce the anti-inflammatory protein pentraxin 3 (PTX3) in response to ex vivo stimulation with lipopolysaccharide (LPS), and if acute aerobic exercise would enhance this PTX3 production capacity. In addition, the inter-relationships of LPS-induced PTX3 with the inflammatory cytokines (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha) were examined. Twenty-one healthy subjects (10 obese and 11 normal-weight) performed an acute bout of aerobic exercise at 75% VO 2max . The capacity of PBMCs to produce PTX3 ex vivo following LPS stimulation was the same in obese and normal-weight subjects at rest, and decreased equally in both subject groups following acute aerobic exercise. This is in contrast to plasma PTX3, which is lower in obese subjects at rest and increased equally in both obese and normal-weight subjects following exercise. In addition, ex vivo PTX3 production was positively associated with IL-6 and IL-10 in response to acute aerobic exercise (r ¼ 0.686, P ¼ 0.020; r ¼ 0.744, P ¼ 0.009, respectively) in normal-weight, but not in obese individuals (r ¼ 0.429, P ¼ 0.249; r ¼ 0.453, P ¼ 0.189, respectively). These findings indicate that concentrations of PTX3 observed in plasma are relatively independent of those produced by PBMCs ex vivo and the mechanisms associated with PTX3-mediated anti-inflammatory signaling may differ during obesity.

Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

“…Similarly, although Osorio-Conles et al [59] demonstrated that PTX3 gene expression is increased and positively associated with the presence of proinflammatory protein expression in mature adipocytes isolated from VAT, plasma PTX3 concentrations are decreased in obese compared to normal-weight individuals. Given the similarities among obesity- and age-related changes in adipose tissue [60] and the positive role that PTX3 has been shown to play in the regulation of appropriate immune function and prevention of CVD and metabolic disease [39, 41, 42, 61–63], plasma PTX3 concentrations were expectedly lower in middle-aged compared to young adults. Therefore, additional research is warranted to determine whether or not lower plasma PTX3 concentrations during middle age are related to morphological changes of VAT or an impairment of neutrophils, the primary cellular source of PTX3, to synthesize and store PTX3 throughout their maturation [64, 65].…”

“…Pentraxin 3 (PTX3) is a counterregulatory protein that is expressed and secreted from isolated leukocytes in concert with various inflammatory proteins (e.g., IL-6, IL-10, TGF- β , and TNF- α ) following LPS stimulation [36–39]. Elevated PTX3 production is required to prevent overactivation of the inflammatory signaling pathway, and increased plasma PTX3 concentrations are considered an indicator of appropriate immune function in young, healthy adults [39–43]. In addition, Pavanello et al [44] have recently demonstrated that elevated concentrations of plasma PTX3 are associated with longer telomere lengths in healthy middle-aged adults.…”

Effects of eccentric exercise-induced delayed onset muscle soreness on endoplasmic reticulum stress-related markers

“…Regular exercise could prevent cardiovascular morbidity by decreasing systematic inflammation, while excess inflammation can be reduced by anti-inflammatory protein PTX3 as well. In their study, Slusher et al (2017) reported that although the basal PTX3 level of obese participants were lower after a single session aerobic exercise performed with 75% of VO 2 max, it remarkably fell immediately after the exercise both in obese and normal-weight participants (p <0.05), and went up to reach the basal values 1 h after the exercise [28].…”

The Effect of All-Extremity High-Intensity Interval Training on Plasma Pentraxin 3 in Young Overweight and Obese Women

“…Also, participating in regular continuous moderate exercise sessions could increase PTX3 in middle-aged women (12). What is more, endurance trained men had higher levels of plasma PTX3 compared to sedentary individuals (13), and acute submaximal aerobic exercise increased PTX3 in healthy obese individuals (14,15). In all of these studies, moderate continuous body weight bearing exercises were practiced.…”