Abstract
Kefir peptides, generated by kefir grain fermentation of milk proteins, showed positive antioxidant effects, lowered blood pressure and modulated the immune response. In this study, kefir peptide was evaluated regarding their anti-inflammatory effects on particulate matter <4 μm (PM4.0)-induced lung inflammation in NF-κB-luciferase+/+ transgenic mice. The lungs of mice under 20 mg/kg or 10 mg/kg PM4.0 treatments, both increased significantly the generation of reactive oxygen species (ROS) and inflammatory cytokines; increased the protein expression levels of p-NF-κB, NLRP3, caspase-1, IL-1β, TNF-α, IL-6, IL-4 and α-SMA. Thus, we choose the 10 mg/kg of PM4.0 for animal trials; the mice were assigned to four treatment groups, including control group (saline treatment), PM4.0 + Mock group (only PM4.0 administration), PM4.0 + KL group (PM4.0 + 150 mg/kg low-dose kefir peptide) and PM4.0 + KH group (PM4.0 + 500 mg/kg high-dose kefir peptide). Data showed that treatment with both doses of kefir peptides decreased the PM4.0-induced inflammatory cell infiltration and the expression of the inflammatory mediators IL-lβ, IL-4 and TNF-α in lung tissue by inactivating NF-κB signaling. The oral administrations of kefir peptides decrease the PM4.0-induced lung inflammation process through the inhibition of NF-κB pathway in transgenic luciferase mice, proposing a new clinical application to particulate matter air pollution-induced pulmonary inflammation.
Highlights
Kg PM4.0 treatments, both increased significantly the generation of reactive oxygen species (ROS) and inflammatory cytokines; increased the protein expression levels of p-NF-κB, NLRP3, caspase-1, IL-1β, TNF-α, IL-6, IL-4 and α-smooth muscle actin (α-SMA)
The NLRP3-inflammasome complex regulates the activation of caspase-1, which catalyzes the cleavage of pro-IL-1β while the NLRP3 inflammasome activates associated speck-like protein (ASC) and caspase-1, which in turn leads to the maturation of the inflammatory cytokines IL-1β and IL-1812
The results suggested that the lung inflammation and fibrosis in the group exposed to the low dose (10 mg/kg) of PM4.0 daily were sufficient, so we choose the low dose of PM4.0 to further evaluate the pulmonary inflammation status after kefir peptides treatment in a preventive animal trial
Summary
Kg PM4.0 treatments, both increased significantly the generation of reactive oxygen species (ROS) and inflammatory cytokines; increased the protein expression levels of p-NF-κB, NLRP3, caspase-1, IL-1β, TNF-α, IL-6, IL-4 and α-SMA. The NLRP3-inflammasome complex regulates the activation of caspase-1, which catalyzes the cleavage of pro-IL-1β while the NLRP3 inflammasome activates ASC and caspase-1, which in turn leads to the maturation of the inflammatory cytokines IL-1β and IL-1812 Both neutrophils and macrophages are important cellular effectors of the innate immune defense, and it is clear that circulating monocytes significantly contribute to the defense against inflammatory reactions[13]. Kefir grains is associated with broad health benefits, since contain a complex of symbiotic components, including lactic acid, acetic bacteria, exopolysaccharide (EPS), and proteins with natural bioactive peptides with a variety of biological activities, such as antimicrobial, immunomodulatory, antiallergenic, antitumoral, antidiabetic, anti-inflammatory, antimutagenic activities and antioxidative effects[14,15,16,17,18,19,20]. In this research was established a PM4.0-induced lung inflammation in transgenic homozygous NF-κB-luciferase+/+ mice model and was evaluated the anti-inflammatory and antioxidant effect of kefir peptide
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