PGE₂ is a potent lipid mediator involved in maintaining homeostasis but also promotion of acute inflammation or immune suppression in chronic inflammation and cancer. Nucleotide-binding domain, leucine-rich repeat–containing protein (NLR)P3 inflammasome plays an important role in host defense. Uncontrolled activation of the NLRP3 inflammasome, owing to mutations in the NLRP3 gene, causes cryopyrin-associated periodic syndromes. In this study, we showed that NLRP3 inflammasome activation is inhibited by PGE₂ in human primary monocyte-derived macrophages. This effect was mediated through PGE₂ receptor subtype 4 (EP4) and an increase in intracellular cAMP, independently of protein kinase A or exchange protein directly activated by cAMP. A specific agonist of EP4 mimicked, whereas its antagonist or EP4 knockdown reversed, PGE₂-mediated NLRP3 inhibition. PGE₂ caused an increase in intracellular cAMP. Blockade of adenylate cyclase by its inhibitor reversed PGE₂-mediated NLRP3 inhibition. Increase of intracellular cAMP by an activator of adenylate cyclase or an analog of cAMP, or a blockade of cAMP degradation by phosphodiesterase inhibitor decreased NLRP3 activation. Protein kinase A or exchange protein directly activated by cAMP agonists did not mimic, and their antagonists did not reverse, PGE₂-mediated NLRP3 inhibition. Additionally, constitutive IL-1β secretion from LPS-primed PBMCs of cryopyrin-associated periodic fever syndromes patients was substantially reduced by high doses of PGE₂. Moreover, blocking cytosolic phospholipase A₂α by its inhibitor or small interfering RNA or inhibiting cyclooxygenase 2, resulting in inhibition of endogenous PGE₂ production, caused an increase in NLRP3 inflammasome activation. Our results suggest that PGE₂ might play a role in maintaining homeostasis during the resolution phase of inflammation and might serve as an autocrine and paracrine regulator.

Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix. During inflammation, there is an increased breakdown of HA, resulting in the accumulation of low molecular weight (LMW) HA and activation of monocytes and macrophages. Eicosanoids, derived from the cytosolic phospholipase A2 group IVA (cPLA2α) activation, are potent lipid mediators also attributed to acute and chronic inflammation. The aim of this study was to determine the effect of LMW HA on cPLA2α activation, arachidonic acid (AA) release, and subsequent eicosanoid production and to examine the receptors and downstream mechanisms involved in these processes in monocytes and differently polarized macrophages. LMW HA was a potent stimulant of AA release in a time- and dose-dependent manner, induced cPLA2α, ERK1/2, p38, and JNK phosphorylation, as well as activated COX2 expression and prostaglandin (PG) E2 production in primary human monocytes, murine RAW 264.7, and wild-type bone marrow-derived macrophages. Specific cPLA2α inhibitor blocked HA-induced AA release and PGE2 production in all of these cells. Using CD44, TLR4, TLR2, MYD88, RHAMM or STAB2 siRNA-transfected macrophages and monocytes, we found that AA release, cPLA2α, ERK1/2, p38, and JNK phosphorylation, COX2 expression, and PGE2 production were activated by LMW HA through a TLR4/MYD88 pathway. Likewise, PGE2 production and COX2 expression were blocked in Tlr4(-/-) and Myd88(-/-) mice, but not in Cd44(-/-) mice, after LMW HA stimulation. Moreover, we demonstrated that LMW HA activated the M1 macrophage phenotype with the unique cPLA2α/COX2(high) and COX1/ALOX15/ALOX5/LTA4H(low) gene and PGE2/PGD2/15-HETE(high) and LXA4(low) eicosanoid profile. These findings reveal a novel link between HA-mediated inflammation and lipid metabolism.

Background: Several studies have shown that following a healthy diet and practicing regular physical activity (PA) are related with multiple health benefits. However, the cognitive and academic implications of these behaviors within adolescents requires further study. Material and Methods: A cross-sectional study was conducted with a simple of 1059 adolescents from Spain. The main instruments employed were the Adherence to Mediterranean Diet Test (KIDMED), the Physical Activity Questionnaire for Adolescents (PAQ-A) and the Motivation and Learning Strategies Short Form (MSLQ-SF). Results: Practicing PA for more than three hours per week was related to better dietary habits (p < 0.001) such as increased consumption of vegetables (0.75 ± 0.43 vs. 0.62 ± 0.48), fish (0.67 ± 0.47 vs. 0.58 ± 0.49), cereals (0.85 ± 0.35 vs. 0.77 ± 0.41) and nuts (0.44 ± 0.49 vs. 0.35 ± 0.47). High adherence to a Mediterranean diet (MD) was positively related to elaboration strategies (r = 0.116), organizational strategies (r = 0.109), critical thinking (r = 0.116), self-regulation (r = 0.159), time and study habits (r = 0.160), self-regulation of effort (r = 0.118), and intrinsically orientated goals (r = 0.090) (p < 0.01 for all variables). Practicing PA every week was also related to improvements in several of the measured variables and in addition was related to lower levels of anxiety within the academic environment (r = −0.070; p < 0.05). Conclusions: Given the benefits of eating habits and the practice of PA in the cognitive processes involved in adolescent learning, intervention programs within the educational context are recommended to improve healthy habits.

The present study set out to define and contrast an explanatory model of perception of stress, the dimensions of burnout syndrome, emotional intelligence, and non-verbal communication in a sample of university teachers. A total of 1316 teachers from Spain, aged between 24 and 70 years (M = 45.64, SD = 10.33) and evenly distributed between both sexes, participated. The measurement instruments employed were the Perceived Stress Scale (PSS), the Maslach Burnout Inventory (MBI), the Trait Meta-Mood Scale (TMMS-24), and the Nonverbal Immediacy Scale (NIS) A structural equation model was produced that demonstrated adequate fit to the empirical data (130,259; df = 9; p < 0.001; CFI = 0.907; NIF = 0.914; IFI = 0.923; RMSEA = 0.077). Results revealed that stress relates positively with emotional exhaustion and negatively with personal fulfilment. Emotional exhaustion was associated directly with emotional attention and inversely with emotional clarity and emotional repair, with these being linked to personal fulfilment. Both emotional clarity and repair related positively with non-verbal communication. Conclusions from the present study are that emotional intelligence and body language are two relevant factors in the prevention of burnout syndrome, and as a result can help to ensure the mental wellbeing of university teachers.