Beta-defensin 102

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2'-fucosyllactose attenuate TLR4 signaling; 3'-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling.

Diabetic kidney disease (DKD) is one of the more limiting complications to the quality of life of diabetes mellitus patients. Studies including cultured cells, animal models, and case-control studies highlight the role of human β-defensin-1 (hBD-1) in diabetes.This study assessed the association of hBD-1 gene (DEFB1) functional variations -52 G/A (rs1799946), -44 C/G (rs1800972) and -20 G/A (rs11362) with type 2 diabetes mellitus (T2DM) in order to investigate its effects on genetic susceptibility and progression to DKD in a Mexican population. A total of 214 T2DM patients with and without DKD (n = 102 and n = 112, respectively) and 117 healthy subjects participated in this case-control study. Genotyping was made by PCR-RFLPs. Clinical and biochemical parameters of all patients were measured. There was no statistically significant difference in genotype or allele frequencies between patients and healthy individuals. Nevertheless, compared with patients without DKD, DKD patients have a reduced prevalence of AA genotype of -52 G/A (OR = 0.307, 95% CI = 0.104-0.905, p =.026), as well as a higher frequency of GA genotype of -20 G/A variant (OR = 1.875, 95%CI = 1.031-3.409, p = .038). Our results suggest that rs1799946 and rs11362 could be useful variants to stratify T2DM Mexican patients in order to prescribe closer follow-up to prevent or retard DKD. Further tests in different ethnic groups are encouraged.

The objective of this study was to evaluate expression of a cluster of genes encoding β-defensin antimicrobial peptides in neutrophils of postpartum cows in relation to prepartum dietary cation-anion difference (DCAD), vitamin D, and postpartum disease. Pregnant dry Holstein cows (28 nulliparous and 51 parous) at 255 d gestation were blocked by parity and randomly assigned to 4 prepartum diets of positive (+130 mEq/kg) or negative (-130 mEq/kg) DCAD and either 3 mg vitamin D3 or 3 mg of 25-hydroxyvitamin D3 per 11 kg of dry matter/d. Treatment diets were fed from 255 d of gestation until calving. Peripheral blood neutrophils of 35 parous cows were collected at 0 and 3 d after calving and stimulated with 0 or 100 ng/mL of lipopolysaccharide (LPS). Furthermore, serum Ca and incidences of postpartum diseases were recorded for all cows. The mRNA transcripts of β-defensin genes were quantified by real-time PCR, and data were analyzed with a general linear mixed model to test for fixed effects and interactions of day, level of DCAD, source of vitamin D, and incidence of disease. Effects of DCAD and vitamin D on neutrophil oxidative burst and phagocytosis were previously reported but were analyzed for effects of disease in the present study. Transcripts for DEFB1, DEFB3, DEFB4, DEFB5, DEFB7, DEFB10, and lingual antimicrobial peptide (LAP) in neutrophils were upregulated by LPS at 0 d but not at 3 d. Transcripts for DEFB4 and DEFB7 in LPS-stimulated neutrophils were greater in cows fed negative DCAD diets compared with positive DCAD. Source of vitamin D (vitamin D3 vs. 25-hydroxyvitamin D3) did not affect expression of β-defensins in neutrophils. Cows with postpartum subclinical hypocalcemia (serum Ca <2.0 mM) had decreased DEFB3, DEFB4, DEFB6, DEFB7, DEFB10, and LAP expression in LPS-stimulated neutrophils compared with cows that did not experience subclinical hypocalcemia. Likewise, DEFB4, DEFB6, DEFB7, DEFB10, and LAP in LPS-stimulated neutrophils at 3 d postpartum were positively associated with serum Ca at 0 d postpartum. Transcripts for DEFB7, DEFB10 and LAP also were less abundant in neutrophils from cows with metritis compared with healthy cows. In conclusion, feeding a prepartum negative DCAD to improve postpartum serum Ca resulted in greater neutrophil β-defensin expression, and greater neutrophil β-defensin expression was positively associated with postpartum health.