β-Defensin 129 Attenuates Bacterial Endotoxin-Induced Inflammation and Intestinal Epithelial Cell Apoptosis

Abstract

Defensins have attracted considerable research interest worldwide because of their potential to serve as a substitute for antibiotics. In this study, we characterized a novel porcine β-defensin (pBD129) and explored its role in alleviating bacterial endotoxin-induced inflammation and intestinal epithelium atrophy. The pBD129 gene was cloned and expressed in Escherichia coli. A recombinant pBD129 protein was also purified. To explore its role in alleviating the endotoxin-induced inflammation, mice, with or without lipopolysaccharide (LPS) challenge were treated by pBD129 at different doses. The recombinant pBD129 showed significant antimicrobial activities against the E. coli and Streptococcus with a minimal inhibitory concentration (MICs) of 32 μg/mL. Hemolytic assays showed that the pBD129 had no detrimental impact on cell viabilities. Interestingly, we found that pBD129 attenuated LPS-induced inflammatory responses by decreasing serum concentrations of inflammatory cytokines, such as the IL-1β, IL-6, and TNF-α (P < 0.05). Moreover, pBD129 elevated the intestinal villus height (P < 0.05) and enhanced the expression and localization of the major tight junction-associated protein ZO-1 in LPS-challenged mice. Additionally, pDB129 at a high dose significantly decreased serum diamine oxidase (DAO) concentration (P < 0.05) and reduced intestinal epithelium cell apoptosis (P < 0.05) in LPS-challenged mice. Importantly, pBD129 elevated the expression level of Bcl-2-associated death promoter (Bcl-2), but down-regulated the expression levels of apoptosis-related genes such as the B-cell lymphoma-2-associated X protein (Bax), BH3-interacting domain death agonist (Bid), cysteinyl aspartate-specific proteinase-3 (Caspase-3), and caspase-9 in the intestinal mucosa (P < 0.05). These results suggested a novel function of the mammalian defensins, and the anti-bacterial and anti-inflammatory properties of pBD129 may allow it a potential substitute for conventionally used antibiotics or drugs.

Reserpine improves Enterobacteriaceae resistance in chicken intestine via neuro-immunometabolic signaling and MEK1/2 activation

“…For example, fowlicidin-1 can neutralize bacterial lipopolysaccharide (LPS) 28 , a microbe-associated molecular pattern that potently induces inflammation 29 . Furthermore, beta-defensins reduce intestinal apoptotic signals in LPS-treated animals 30 . Thus, improving the production of these AMPs may both increase resistance against bacterial pathogens, as well as mitigate host damage induced by these antibacterial responses.…”

Mechanisms of action of anti-inflammatory proteins and peptides with anti-TNF-alpha activity and their effects on the intestinal barrier: A systematic review

“…Xie et al [ 40 ] evaluated the preventive action of pig β-defensin 129 (pBD129) in mice that received intraperitoneal LPS. The results showed that this β-defensin also attenuated the inflammatory response and mucosal atrophy by reducing the secretion of inflammatory cytokines and the apoptosis of intestinal epithelial cells, which indicates antibacterial and anti-inflammatory properties.…”

Pigs Overexpressing Porcine β-Defensin 2 Display Increased Resilience to Glaesserella parasuis Infection

“…As regards viable alternatives to antibiotics, defensins have been reported to have effective antimicrobial activities against infectious agents, including bacteria. Within the 29 porcine β-defensins discovered so far, the antibacterial activities of porcine β-defensin 1, PBD-2, and porcine β-defensin 129 have been well described [ 6 , 38 , 39 ]. Notably, since the discovery of PBD-2 in 2006 via sequence similarity analysis [ 40 ], PBD-2 has been the most studied porcine defensin regarding its antibacterial property.…”