Milk modulates macrophage polarization in vitro

Abstract

Objective Milk holds an anti-inflammatory response that is particularly important to protecting infants against necrotizing enterocolitis. Milk might also exert anti-inflammatory effects in adulthood, including the oral cavity where macrophages of the oral mucosal control innate immunity defense. It remains unknown, however, whether milk can modulate the local inflammatory response by affecting the polarization of macrophages. Material and Methods To determine whether pasteurized human milk and pasteurized cow milk can provoke macrophage polarization, murine bone marrow macrophages and RAW264.7 cells were exposed to human saliva or the inflammatory cytokines IL1β and TNFα. Activation of pro-(M1) inflammatory response is indicated by the expression of IL1 and IL8. To determine polarization towards a M2 phenotype, the expression of arginase 1 (ARG1) and chitinase-like 3 (Chil3) was determined by reverse transcriptase PCR and immunoassay. Western blot was done on phosphorylated p38 and JNK. Results Aqueous fractions of human milk and cow milk from different donors, respectively, significantly decreased the inflammatory response of primary macrophages and RAW264.7 cells when exposed to saliva or IL1 and TNFα. Similar to IL4, human milk and cow milk caused a robust expression of ARG1 and Chil3 in primary macrophages. The polarization of macrophages by pasteurized milk occurred independent of the phosphorylation of p38 and JNK. Conclusion These data suggest that pasteurized milk, independent of the origin, can cause the polarization of macrophages from a pro-inflammatory M1 towards a pro-resolving M2 phenotype. Thus, milk might have a protective role for the oral cavity by modulation of the macrophage-based innate immune system.

Hypoallergenic infant formula lacks transforming growth factor beta activity and has a lower anti-inflammatory activity than regular infant formula

“…Even though oral mucosal healing was considered the ideal system of wound resolution (Iglesias-Bartolome et al, 2018), oral mucositis is a frequent and severe complication of chemotherapy in children (Cheng et al, 2008) and adults with cancer (Lalla et al, 2014). Considering that milk comes into contact with the oral mucosa, we have recently confirmed TGF-β and antiinflammatory activity of milk in bioassays representing oral fibroblast and oral epithelial cells (Panahipour et al, 2018b(Panahipour et al, , 2019 and macrophages that are highly abundant in the oral mucosa (Panahipour et al, 2018a). We further confirmed the anti-inflammatory activity of regular formula, but not the respective TGF-β activity (Panahipour et al, 2019).…”

“…Based on our recent observations that milk has a clear anti-inflammatory activity in primary macrophages (Panahipour et al, 2018a), it was reasonable to investigate whether the findings can be reproduced with RF and HAF. We showed that 1% RF greatly suppressed the saliva-induced inflammatory response in primary macrophages: RF reduced expression of IL-1 and IL-6, with 35.0 and 21.0% expression remaining (median values), respectively, compared with 100% stimulated controls (Figure 5C).…”

Macrophages and the maintenance of homeostasis

“…12 They also exert regulatory functions with important roles in the control of inflammation and the promotion of healing responses in newborns. 13 Indeed, macrophages are the only cells present in every organ in the body. Macrophages are present in the epidermis, cornea, and the insides of joints, where blood vessels do not exist.…”

The Potential of lactoferrin, Ovotransferrin and Lysozyme As Antiviral and immune-modulating Agents in COVID-19

“…Lactoferrin suppresses extracellular traps released by neutrophils during inflammation [ 68 ], and has also been shown to stimulate pro-inflammatory macrophages (M1) to change to the anti-inflammatory macrophages (M2) type [ 43 , 66 ]. Similarly, pasteurized whole cow’s milk has been shown to polarize macrophages from M1 toward a proresolving M2 phenotype [ 97 ]. In addition, lactoferrin-derived peptides inhibit angiotensin II pro-inflammatory activity through binding to the angiotensin II receptor type 1 [ 69 ], and lactoferrin as well as other peptides in cow’s milk have an antithrombotic effect [ 71 ].…”

“…It is further suggested that, in the current circumstances of the COVID-19 pandemic, good quality nonisolated forms of these (such as egg white powder, bovine colostrum powder and other nonultrahigh temperature milk products with appreciable lactoferrin content) should also be tested while ensuring the desired concentrations of each antimicrobial are met, especially in settings where the isolated forms may not be as readily accessible. In favor of this suggestion, studies using lactoferrin-containing milk or lactoferrin-supplemented yoghurt have shown clinical efficacy in viral diseases [ 107 , 178 ], pasteurized whole milk has shown the effect of switching macrophages from M1 to M2 [ 97 ], several peptides in milk are antithrombotic [ 71 ], and several peptides in egg white besides those in ovotransferrin show supportive antioxidant as well as ACE-inhibitory effects [ 79 , 111 ]. However, in those individuals who are already critically ill and on ventilators, more care may need to be taken with the approach.…”