Kefir peptides alleviate particulate matter <4 μm (PM4.0)-induced pulmonary inflammation by inhibiting the NF-κB pathway using luciferase transgenic mice

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 (PM 4.0 )-induced lung inflammation in NF-κB-luciferase +/+ transgenic mice. The lungs of mice under 20 mg/kg or 10 mg/kg PM 4.0 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 PM 4.0 for animal trials; the mice were assigned to four treatment groups, including control group (saline treatment), PM 4.0 + Mock group (only PM 4.0 administration), PM 4.0 + KL group (PM 4.0 + 150 mg/kg low-dose kefir peptide) and PM 4.0 + KH group (PM 4.0 + 500 mg/kg high-dose kefir peptide). Data showed that treatment with both doses of kefir peptides decreased the PM 4.0 -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 PM 4.0 -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.

Anti-Inflammatory, Antioxidant, and Antifibrotic Effects of Kefir Peptides on Salt-Induced Renal Vascular Damage and Dysfunction in Aged Stroke-Prone Spontaneously Hypertensive Rats

“…The kefir-fermented product derived from a milk protein source used in this study to determine the potential role of KPs in the management of salt-induced chronic kidney disease contained 15.48 g/100 g peptide, and its main components are listed in Supplementary Table S1 . The reproducibility of the prepared kefir peptides was high, as shown in our previous study [ 16 , 19 , 20 ].…”

“…After sacrificing the rats, the upper lateral half of the kidney tissue was freshly dissected. These tissues were fixed in 10% buffered formaldehyde (pH 7.0), embedded in paraffin, sectioned into 3 μm sections, and processed for three types of histopathological stains: hematoxylin and eosin (H&E) [ 19 ], Masson’s trichrome [ 20 ] and Sirius red [ 25 ]. The severity of the observed lesions was graded by a pathologist according to the standard method [ 26 ].…”

Kefir: A protective dietary supplementation against viral infection

“…Many of these byproducts may have extensive outcomes in the host without the presence of a microbial community [ 48 ]. Chen et al studied the anti-inflammatory and antioxidant activities of kefir peptides against particulate material smaller than 4 μm (PM 4.0 )-induced lung inflammation in transgenic homozygous nuclear factor-kappa B (NF-κB)-luciferase +/+ mice [ 27 ]. They demonstrated that kefir peptides had potent anti-inflammatory effects through reduction of expression of the proinflammatory cytokines IL-lβ, IL-4, IL-6 and TNF-α in lung tissue by inhibition of NF-κB signalling.…”

“…Kefir has been shown to inhibit angiotensin-converting enzyme (ACE) levels, cholesterol metabolism, accelerate wound healing, suppress tumour growth, and cause alterations in the immune system to improve asthma symptoms and allergy [ [22] , [23] , [24] , [25] ]. Kefir and kefir derivatives (e.g., polysaccharides, protein, peptides) can suppress viral activity by modulating immune-system responses and/or causing disruption of viral adhesion [ 26 , 27 ]. They also act as anti-inflammatory agents by inhibiting the activity of proinflammatory cytokines such as IL-1β, tumour necrosis factor (TNF)-α and IL-6 [ 27 ].…”

“…Kefir and kefir derivatives (e.g., polysaccharides, protein, peptides) can suppress viral activity by modulating immune-system responses and/or causing disruption of viral adhesion [ 26 , 27 ]. They also act as anti-inflammatory agents by inhibiting the activity of proinflammatory cytokines such as IL-1β, tumour necrosis factor (TNF)-α and IL-6 [ 27 ]. Hence, kefir and its byproducts could be employed as protective agents against viral infections.…”