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  • The IL family consists of nine

    2020-01-14

    The IL-10 family consists of nine related molecules: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28α, IL-28β, and IL-29 [34]. These molecules have a somewhat conserved primary structure and contain a core of hydrophobic 4μ8C and two pairs of disulfide bonds in the chain, giving them a similar spatial conformation and thus enabling them to bind type II cytokine receptors [35]. Among these IL-10 family members, IL-10 and IL-22 were reported to be closely related to AD. The expression of IL-10 in AD is controversial. There was only one early article that reported that IL-10 was decreased in a pig AD model [15], while an opposing trend was observed in human AD among other studies [23, [36], [37], [38], [39], [40], [41]]. In addition, using an Ang II-induced mouse AD model, IL-10 could play an anti-inflammatory role and alleviate the progression and development of AD [42]. In our previous study, we found that plasma IL-22 levels were increased in AD patients, and higher aortic IL-22 levels were also observed in the torn section [30]. In another recently published paper, we found that both Th22 and IL-22 levels were increased in AD patients and were positively correlated with the occurrence of AD [21]. All IL-12 superfamily members are heterogenous dimers composed of two subunits, each of which has structural homology. These superfamily members include IL-12, IL-23, IL-27, IL-35 and IL-39 [43, 44]. There are less studies of these superfamily members not only with regard to AD but also other vascular diseases. Our previous study is the only one to observe that both the Treg cell and its functional cytokine IL-35 decrease in AD patients, and this decrease was negatively correlated with the onset of AD [21]. The IL-17 superfamily includes six members, IL-17A, IL-18B, IL-17C, IL-17D, IL-17E (also named IL-25) and IL-17F. IL-17A was the first member of the IL-17 superfamily to be discovered and is commonly known as IL-17 [45]. Of these superfamily members, only IL-17 was found to be critically related to AD. A previous study reported that IL-6 aggravated Ang II-induced mouse AD via the promotion of Th17/IL-17 secretion [31]. Our recent study found that circulating Th17/IL-17 levels were elevated in AD patients [21, 30]. There are other ILs that are not included in these six superfamilies, including IL-3, IL-8, IL-13, IL-14, IL-16, IL-32, IL-34 and IL-40. IL-3 is a colony 4μ8C stimulating factor and is also named multi-colony stimulating factor (multi-CSF) and hemopoietic cell growth factor (HCGF). In a recent study, Liu C et al. reported that IL-3 expression was up-regulated in a BAPN-induced mouse AD model and that SMCs were the main course of action. IL-3 activated the c-Jun N-terminal kinase (JNK)- and extracellular regulated protein kinases (ERK)-dependent activator protein 1 (AP-1) pathway in macrophages, stimulated matrix metalloproteinase (MMP) 12 production and contributed to TAAD formation. Knockout of IL-3 significantly reduced MMP12 expression in the aortic wall and reduced protease activity; this was associated with protection against AD [46, 47]. IL-8 is an important chemokine and has been demonstrated to be involved in AD [48]. Increased IL-8 expression was observed in both blood and aorta samples from AD patients [23, 36, 49, 50]. Plasma IL-16 levels were reported to be elevated in AD patients [51]. The role of IL-13, IL-14, IL-32, IL-34 and IL-40 in AD has not yet been observed.
    The role of IFNs and AD IFNs can be divided into three distinct types, namely, type-I, type-II and type-III [52]. Type-I IFN members include 14 genes, such as the well-known IFN-α and FN-β and the lesser understood IFN-ε, IFN-κ, and IFN-ω. Type-II IFN consists of one member-IFN-γ, which is biologically and genetically distinct from other IFNs. Type-III IFNs were more recently described, and the members include IFN-λ1, IFN-λ2, IFN-λ3 (which are also named IL-29, IL-28α, and IL-28β, respectively) and IFN-λ4 [53, 54]. Of these IFNs, only IFN-γ was reported to participate in AD. We and other researchers had reported that circulating IFN-γ levels were increased in human AD patients [16, 23, 24, 33]. In our previous study, we found that IL-11 expression also increased in human aortas and that aortic macrophages were an important source [33]. We also found that both Th1 and IFN-γ increased in AD patients and were positively correlated with the occurrence of AD [21]. In addition, increased IFN-γ levels were observed in a rat AD model [55].