Procyanidin A2 Modulates IL-4-Induced CCL26 Production in Human Alveolar Epithelial Cells

Abstract

Allergic asthma is an inflammatory lung disease that is partly sustained by the chemokine eotaxin-3 (CCL26), which extends eosinophil migration into tissues long after allergen exposure. Modulation of CCL26 could represent a means to mitigate airway inflammation. Here we evaluated procyanidin A2 as a means of modulating CCL26 production and investigated interactions with the known inflammation modulator, Interferon γ (IFNγ). We used the human lung epithelial cell line A549 and optimized the conditions for inducing CCL26. Cells were exposed to a range of procyanidin A2 or IFNγ concentrations for varied lengths of time prior to an inflammatory insult of interleukin-4 (IL-4) for 24 h. An enzyme-linked immunosorbent assay was used to measure CCL26 production. Exposing cells to 5 μM procyanidin A2 (prior to IL-4) reduced CCL26 production by 35% compared with control. Greatest inhibition by procyanidin A2 was seen with a 2 h exposure prior to IL-4, whereas IFNγ inhibition was greatest at 24 h. Concomitant incubation of procyanidin A2 and IFNγ did not extend the inhibitory efficacy of procyanidin A2. These data provide evidence that procyanidin A2 can modulate IL-4-induced CCL26 production by A549 lung epithelial cells and that it does so in a manner that is different from IFNγ.

Procyanidin A2, a polyphenolic compound, exerts anti-inflammatory and anti-oxidative activity in lipopolysaccharide-stimulated RAW264.7 cells

“…On the other hand, LPS-stimulated macrophage is a classic model of inflammatory responses in vitro [ 33 ]. Previous studies revealed that PCA2 has the effects of protecting cells from oxidation, inflammation, such as human monocyte macrophages (THP-1) [ 26 ] and L0-2 cells [ 35 ], A549 cells [ 24 ], and BV2 cells [ 36 ], respectively. PCA2 exhibited anti-inflammatory activity via suppressing CCL-26 production in IL-4-stimulated A549 cells [ 24 ] and anti-oxidative activity via modulating the Nrf2 pathway in tert -butyl hydroperoxide-stimulated L0-2 cells [ 35 ].…”

“…Procyanidin, polyphenolic secondary metabolites, is a compound formed by the polymerization of flavan-3-ol as a structural unit through C-C bond, and its mechanism is currently unclear [24]. Procyanidin A2 (PCA2) is an A-type proanthocyanidin dimer formed by the polymerization of epicatechin ( Fig 1A) and preponderantly locate in the nucleus, shell, seed, flower, and leaves of many plants [24]. Specifically, the content of PCA2 is occupies a large percentage in grape seeds [25].…”

Immune-Boosting Functional Foods: A Potential Remedy for Chinese Consumers Living Under Polluted Air

“…Compounds reported to have immune enhancing properties include food ingredients or are found in natural immune-boosting whole foods. In addition, many studies are working on identifying plant compounds that target specific cellular events and complement the body's own immune actions upon exposure to known allergens such as air pollution (Coleman, Kruger, Sawyer, & Hurst, 2016;Sawyer, Stevenson, McGhie, & Hurst, 2017). In any event it is likely that the results from such research will support the development of functional foods with beneficial biological activities to help the immune system recover from the impact of air pollution (Nyanhanda et al, 2014).…”

Boysenberry and apple juice concentrate reduced acute lung inflammation and increased M2 macrophage‐associated cytokines in an acute mouse model of allergic airways disease

“…These dietary‐related improvements in lung function benefits are also seen in people living in polluted environments (Burbank et al., 2018; Pounis et al., 2018; Stevens et al., 2019). Fruits and vegetables contain numerous bioactive compounds, including anthocyanins and procyanidins, which have been shown to attenuate lung inflammation in cell and animal models of allergy and asthma (Coleman et al., 2016; Coleman & Shaw, 2017; Park et al., 2007; Sawyer et al., 2017; Shaw et al., 2016, 2017). Human population studies have identified that dietary intake of foods high in polyphenols and tetraterpenes (Pounis et al., 2018) such as apples, pears (Garcia‐Larsen et al., 2018), carrots, tomatoes (Rosenlund et al., 2011), and citrus is inversely correlated with the frequency and severity of reported asthma symptoms, especially wheezing and coughing (Garcia et al., 2005; Garcia‐Larsen et al., 2018; McKeever & Britton, 2004; Rosenlund et al., 2011).…”