Cross-Talk between Apolipoprotein E and Cytokines

Abstract

Apolipoprotein E (apoE) is a multifunctional glycosylated protein characterized by its wide tissue distribution. Despite its importance in lipid transport and atherosclerosis pathogenesis, apoE is associated with neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson disease, and autoimmune disorders such as multiple sclerosis and psoriasis. Among others, the role of apoE in modulating inflammation and oxidation is crucial in elucidating the risk factors of the above diseases since the function of apoE is closely linked with both proinflammatory and antiinflammatory cytokines. Moreover, apoE modulates inflammatory and immune responses in an isoform-dependent manner. Correspondingly, inflammatory cytokines can either upregulate or downregulate the production of apoE in various tissue types. However, studies on the interactions between apoE and cytokines occasionally yield conflicting results, highlighting the complex roles of apoE and cytokines in various disorders. The present paper summarizes the current knowledge about the cross-talk between apoE and cytokines, with emphasis on the effects of apoE on the Th1/Th2 balance.

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

“…For instance, we and others have reported that the apoCI apolipoprotein may augment the general inflammatory state 41e44 . ApoE has also been implicated in systemic inflammatory processes, although it can exert both anti-and proinflammatory actions depending on the specific isoform 45,46 . Alternatively, the higher male susceptibility may also be explained by higher androgen levels, which exacerbate OA in mice 47 .…”

“…Human studies also support a role of sex hormones in OA, showing increased OA prevalence and severity in postmenopausal women compared with premenopausal women and age-matched men 48,49 . Moreover, androgens and ApoE isoforms have been shown to be functionally intertwined in inflammatory processes 46,50 , providing a possible rationale as to why ApoE*3Leiden.CETP males show more cartilage degradation in response to metabolic challenges compared with females. Contrary to the males, female ApoE*3Leiden.CETP transgenic mice showed less cartilage degradation on chow but were susceptible to diet-induced OA.…”

Positive association of Apolipoprotein E4 polymorphism with recurrent pregnancy loss in Iranian patients

“…Apo E, a glycoprotein, is expressed in numerous tissues within body [11]. Its different genotypes are related to the lipid concentration level and have already been implicated as association risk factors in cardiovascular disorders, strokes, Alzheimer disease and as susceptibly factor in response to viral, bacterial and parasitic infection [14]. Compared to E3, the most frequent allele, E4 allele of Apo E has a less affinity for LDL receptor which leads to decreased affinity for collection of chylomicrons from blood circulation [18].…”

“…For a successful pregnancy there should be equilibrium between inflammatory agents and anti-inflammatory cytokine factors [21]. Interleukin 10 (IL10) is the most potent amongst antiinflammatory factor [14]. It has been shown that in carriers of allele E4, IL10 plasma concentration is reduced [22].…”

“…The structural differences of these isoforms determine their function with regard to lipid metabolism [13]. Relationships between Apo E polymorphisms and lipid metabolism have been extensively studied in cardiovascular and neurodegenerative disorders such as Alzheimer disease and Parkinson disease and allele E4 has been implicated as risk factor in these conditions [14]. In normal pregnancy the cholesterol level is naturally increased and as a result Apo E could be involved [15].…”