Defensin, beta 4

Human beta defensin 4 belongs to the large group of antimicrobial peptides (AMP), a heterogeneous group of naturally occurring small (< 100 amino acids), cationic amphiphilic peptides with broad microbicidal activity, known as "endogenous antibiotics". Antimicrobial peptides are synthesized by plants, bacteria, insects, invertebrates and vertebrates.

Human antimicrobial peptides play a major role in the innate, non-specific immune defence (see below immunity, innate) within the framework of an epithelial barrier function in the respiratory, urogenital and gastrointestinal tracts as well as in the skin in defending against infectious pathogens. In addition to the cellular epithelial barrier they represent a kind of chemical barrier. Besides their direct antimicrobial functions they also act as moderators of inflammatory processes.

All beta-defensins have antimicrobial properties in common. They contain a stable cysteine motif. Defensins are thought to fight pathogens by forming pores in the cell wall (Sudheendra US et al. 2015), which leads to a loss of membrane stability and ultimately to the death of the pathogen (see below antimicrobial peptides). The members of this defensin family have similar protein sequences.

Beta-Defensin 4 (BD-4) is a cysteine-rich, human, cationic, amphiphasic, antimicrobial peptide with a dimeric structure. The peptide consists of 51 amino acids with 4 disulphide bridges that give the molecule antimicrobial activity and stability (Sharma H et al. 2015). Beta-defensin 4 is encoded by the DEFB4 gene (also called DEFB103), which is located on the short arm of the 8th chromosome (8p23.1).

The features of Defensin beta 4 (hBD4) still require further exploration. HBD-4 shows high antimicrobial activity against Pseudomonas aeruginosa. However, it is not expressed in keratinocytes (Smiley AK et al. 2007)

In skin biopsies of patients with acrodermatitis papulosa eruptiva infantilis (Gianotti-Crosti syndrome), however, the detection of human defensin beta 4 could be performed in the stratum corneum, the stratum granulosum, and the stratum spinosum (Caltabiano R et al. 2013). This finding suggests that under certain pathological conditions the epidermis is capable of expressing this defensin. HBD-4 is also inhibited by (bacterial) inflammatory activated bronchial epithelia. The levels are significantly higher than in the control cultures (Yanagi S et al. 2005)

Furthermore, HBD-4 is overexpressed in fibroblasts of burn patients (Noronha SA et al. 2014).

Experimentally, defensin beta 4 has been shown to be a concentration-dependent stimulator of cell proliferation and cell viability in some carcinoma cell lines. Furthermore, it leads to an increase in tumor cell mobility (Gerashchenko OL et al. 2013).

Furthermore, it could be shown experimentally that beta-defensins 1 and 4, but not defensin beta 2 are expressed in cell cultures of follicular, papillary and undifferentiated (analplastic) thyroid carcinomas (C73). The treatment of the cultures with defensin beta 2 led to a suppression of tumor cell growth depending on the concentration.

1. Caltabiano R et al.(2013) Human β-defensin 4 expression in Gianotti-Crosti. Acta dermatovenerol Croat 21:43-47.
2. Gerashchenko OL et al.(2013) Biologic activities of recombinant human beta-defensin-4 towards cultured human cancer cells. Exp Oncol 35:76-82.
3. Noronha SA et al (2014) Human beta defensin-4 and keratinocyte growth factor gene expression in cultured keratinocyte and fibroblasts of burned patients. Acta Cir Bras 29 Suppl3:39-43.
4. Sharma H et al (2015) Human β-defensin 4 with non-native disulfide bridges exhibit antimicrobial activity. PLoS One 10:e0119525.
5. Smiley AK et al (2007) Expression of human beta defensin 4 in genetically modified keratinocytes enhances antimicrobial activity. J Burn Care Res 28:127-132. Yanagi S et al. (2005)
6. Isolation of human beta-defensin-4 in lung tissue and its increase in lower respiratory tract infection Respir Res 6:130.
7. Zhuravel OV et al (2014) Expression of human beta-defensins-1-4 in thyroid cancer cells and new insight onbiologic activity of hBD-2 in vitro. Exp Oncol 36:174-178.