In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers.

In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 µg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent Clostridium perfringens strain for three days. To investigate IL-17-mediated effects against C. perfringens infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 µg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 µg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In C. perfringens-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 µg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with C. perfringens.

Association between DEFB1 rs11362 and Caries Susceptibility in Permanent Dentition: A Cross Sectional Study.

BACKGROUND: Dental caries is a multifactorial chronic bacterial infectious disease. Variations in the predisposition of the general population to dental cavities suggest that genetic and immunological factors play significant roles in its pathogenesis. This study aims to explore the impact of the Beta-Defensin 1 (DEFB1) rs11362 polymorphism on caries susceptibility in permanent dentition among the Bai Kuyao and Zhuang ethnic groups in China. METHODS: A sample of 754 adolescents aged 12-15 was randomly selected from primary and junior high schools in Nandan County, Guangxi, China. All adolescents underwent clinical examinations, and DNA samples were collected. The genotype of DEFB1 rs11362 was determined using single nucleotide polymorphism (SNP) typing. The concentration of human ß Defensin 1 (hBD-1) protein in saliva was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The distribution of the DEFB1 rs11362 T allele was lower in the Bai Kuyao group compared to the Zhuang group. The disparity in the rs11362 genotype was statistically significant in the superficial dentin caries subgroup of the Bai Kuyao population (p = 0.017). Following adjustment for all potential confounding variables, the analysis revealed a heightened risk of superficial dental caries among CT genotype carriers in the Bai Kuyao population under a co-dominant model (odds ratios (OR) = 2.70; 95% confidence intervals (CI) [1.35-5.44]; p = 0.005), and an increased risk among CC genotype carriers in the Bai Kuyao population under a dominant model (OR = 2.35; 95% CI [1.18-4.67]; p = 0.015). A significant difference (p < 0.05) was noted in the distribution of rs11362 genotypes and salivary hBD-1 levels among the Bai Kuyao group. Salivary hBD-1 levels were notably higher in the CC genotype group (4.12 ± 2.07 ng/mL) compared to both the CT (2.77 ± 1.62 ng/mL) and TT genotype groups (2.32 ± 0.98 ng/mL). CONCLUSION: The DEFB1 rs11362 polymorphism showed an association with caries susceptibility in permanent teeth and influenced hBD-1 protein expression in saliva. Consequently, the DEFB1 polymorphism likely represents a concealed risk factor for caries.

Human ß-defensin 2: a connection between infections and allergic skin diseases.

Beta defensins (ß-defensins) are peptides primarily produced by epithelial cells in mammals to safeguard the skin, other organs, and mucosa from microbial colonization. These peptides are generated by epithelial cells, keratinocytes, and macrophages, mainly in response to interactions with microorganisms (bacteria, viruses, and fungi) or the influence of various pro-inflammatory cytokines. Human ß-defensin (HBD) 2 plays an indirect role in allergic reactions by promoting mast cell activation and degranulation. In dermatological and allergic conditions, the role of HBD2 has been well documented. Although HBD2 is predominantly produced in keratinocytes, along with HBD3 it has also been detected in serum. Elevated serum levels of HBD2 have been observed in patients with skin diseases such as atopic dermatitis and psoriasis. In addition, HBD2 is significant in chronic spontaneous urticaria (CSU), in which urticarial skin lesions can be triggered by infections. Notably, CSU is often accompanied by angioedema, which may be related to HBD2 because patients with CSU and associated angioedema have higher serum HBD2 levels compared to those without angioedema. Current evidence suggests that HBD2 could serve as a marker of inflammation and may have potential therapeutic applications. However, due to limited data on HBD2 levels and its expression in the skin of patients with allergic skin diseases, further research is needed to elucidate the underlying causes and mechanisms of elevated HBD2 levels in these conditions.

Analyzing the morphology and avian ß-defensins genes (AvßD) expression in the small intestine of Cobb500 broiler chicks fed with sodium butyrate.

BACKGROUND: Sodium butyrate is a potential antibiotic growth promoter and has had advantageous effects on the poultry industry. METHODS: Evaluating the effect of sodium butyrate on the intestinal villi and the humoral part of innate immunity of the male Cobb 500 broiler using scanning electron microscopy and quantitative real-time PCR analysis, the control group and treated group of Cobb 500 with SB supplemented received water containing 0.98 mg sodium butyrate. RESULTS: The administration of sodium butyrate changed the villi characters, as the shape changed from tongue to long tongue. They were mainly parallel to each other and long finger-like at the duodenum. The tips of the villi in the control group appeared thin-slight curved with a prominent center in the duodenum, thin rectangular in the jejunum, and ileum in the control group. In contrast, in the treatment group, they changed to thick rectangular in the duodenum and ileum zigzag shape in the jejunum. The epithelium lining of the duodenal villi showed a dome shape, the jejunal villi showed a polygonal shape, and the ileal villi appeared scales-like. The epithelium lining showed irregular microfolds and many different-sized pores, and the treatment group showed islands of long microvilli in the duodenum and solitary long microvilli in the ileum. Real-time PCR of AvBD 1, 2, 10, and 12 significantly (P < 0.01). The better expression of AvBD 1, 2, and 12 was determined in the duodenum, while AvBD 10 was in the jejunum. CONCLUSION: Sodium butyrate enhanced the chicks' growth and small intestine parameters, modified the morphology of the intestinal villi, and improved the humoral part of innate immunity.

Human Beta Defensin-2 mRNA and Proteasome Subunit ß Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients.

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human ß-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies.

Alpha/beta-defensins influence on the humoral immunity and complications in cancer of the oral cavity and oropharynx.

Aim: Patients with cancer of the oral cavity and oropharynx (COCO) often exhibit signs of immunosuppression, affecting their prognosis. Understanding the dynamics of humoral immunity in these patients during chemoradiation therapy is crucial for developing effective treatments.Materials & methods: This prospective study included 105 COCO patients undergoing different treatment regimens, with or without alpha/beta-defensins therapy. Serum concentrations of IgG, IgM, IgA and salivary sIgA were analyzed. Patients were divided into five groups based on treatment protocols.Results & conclusion: Treatment variations impacted serum immunoglobulin levels, notably in Group III, whose patients received radiation treatment and immunotherapy with higher alpha/beta-defensins doses. Significant IgG changes correlated with oral mucositis risk and outcomes. Further trials are necessary for validation and clinical application.

What is this article about? This article examines how different treatments affect the immune system in patients with oral cavity and oropharynx cancer. Specifically, it looks at the levels of certain immune proteins during treatment.What were the results? The study found that patients receiving higher doses of a specific treatment had higher levels of immune proteins in their blood. However, overall, there were no significant changes in the immune system.What do the results of the study mean? While the study did not show major changes in the immune system, it suggests that the treatment may help reduce complications from cancer treatment. However, more research is needed to confirm these findings and understand their impact on patient care.

Restoration of the Lost Human Beta Defensin-1 Protein in Cancer as a Strategy to Improve the Efficacy of Chemotherapy.

Both innate and adaptive immunity are important components of the human defense system against various diseases including cancer. Human beta defensin-1 (hBD-1) is one such immunomodulatory peptide which is lost in malignant cancers, while high levels of expression are maintained in benign cells, making it a potential biomarker for the onset and metastasis of the disease. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer for which no targeted therapy has been approved so far. That makes chemotherapy a first line of treatment despite high side effects. A priori Activation of Apoptosis Pathways of Tumor often referred to as AAAPT technology is a novel targeted tumor sensitizing technology that sensitizes low responsive and resistant tumor cells to evoke a better response from the current treatments for TNBC. Here, we show that hBD-1 is a targeted tumor sensitizer.

Effects of Ellagic Acid on Vaginal Innate Immune Mediators and HPV16 Infection In Vitro.

Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both hBD2 mRNA (mean 2.9-fold at 12.5 µM EA, p < 0.001) and protein (mean 7.1-fold at 12.5 µM EA, p = 0.002) in response to EA. SLPI mRNA also increased significantly (mean 1.4-fold at 25 µM EA, p = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC20 and CC50 showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.

Resveratrol Has Histone 4 and Beta-Defensin 1-Mediated Favorable Biotherapeutic Effects on Liver and Other Target Organs in Diabetic Rats.

BACKGROUND/AIMS:  It was aimed to investigate the biochemical and histopathological effects of resveratrol and melatonin, via histone H4 and ß-defensin 1, in diabetic rats. MATERIALS AND METHODS:  Twenty-four Sprague-Dawley male rats were categorized into 4 groups, with 6 rats in each group (control, diabetes mellitus, melatonin - diabetes mellitus, and resveratrol+diabetes mellitus). Diabetes was formed by giving streptozotocin to all groups except the control group. Melatonin, 5 mg/kg/day, was given to the melatonin - diabetes mellitus group, and resveratrol, 5 mg/kg/day, was given to the resveratrol+diabetes mellitus group via intraperitoneally for 3 weeks. Interleukin-1 beta, tumor necrosis factor alpha, histone H4, and ß-defensin 1 levels were measured in the blood of all rats. The lung, liver, and kidney tissue of all rats were performed as histopathological examinations. RESULTS:  Whereas there was no difference between the other groups (P >.05), interleukin-1 beta levels of the diabetes mellitus group were found to be significantly higher compared with the control group (5.02 ± 2.15 vs. 2.38 ± 0.72 ng/mL; P < .05). Whereas histone H4 levels of the diabetes mellitus group were higher compared with the control and resveratrol+diabetes mellitus groups (7.53 ± 3.30 vs. 2.97 ± 1.57 and 3.06 ± 1.57 ng/mL; P <.05), the ß-defensin 1 levels of the diabetes mellitus group were lower compared with control and resveratrol+diabetes mellitus groups (7.6 ± 2.8 vs. 21.6 ± 5.5 and 18.8 ± 7.4 ng/mL; P <.05). ß-Defensin 1 levels were moderately inversely correlated with interleukin-1 beta and histone H4 levels (rs > -0.50, P < .01). Histopathological changes found in favor of target cell damage in the diabetes mellitus group were not observed in resveratrol+diabetes mellitus group. CONCLUSION:  Resveratrol may be used as a biotherapeutic agent, which significantly reduces diabetes-induced histone H4 and interleukin-1 beta-mediated liver and other target organ damage.

Porcine beta defensin 2 attenuates inflammatory responses in IPEC-J2 cells against Escherichia coli via TLRs-NF-κB/MAPK signaling pathway.

BACKGROUND: Porcine beta defensin 2 (pBD2) is one of the porcine beta defensins that has antibacterial activity, and plays an important role in the immunomodulatory activity that protects cells from pathogens. It has been reported that pBD2 plays their immunomodulatory functions related to the TLR4-NF-κB signal pathways. However, it is not completely clear how pBD2 reduces the inflammatory response caused by pathogens. RESULTS: In this study, the effect of pBD2 on the expression of genes in the TLRs signaling pathway was investigated after IPEC-J2 cells were challenged with E. coli. The results showed that pBD2 decreased the expression of IL-8 induced by E. coli (P < 0.05), and pBD2 significantly decreased the expression of TLR4, TLR5 and TLR7 (P < 0.05), as well as the key downstream genes p38 and JNK which activated by E. coli (P < 0.05). In addition, pBD2 inhibited the p-p65, p-p38 and p-JNK which were up-regulated by E. coli. CONCLUSIONS: pBD2 could reduce the inflammatory response induced by E. coli perhaps by inhibiting the TLRs-TAK1-NF-κB/MAPK signaling pathway which was activated by E. coli in IPEC-J2 cells. Our study further reveals the immunomodulatory activity of recombinant pBD2 against E. coli, and provides insights into the molecular mechanisms that protect cells from E. coli infection.