Defensin, beta 2

Human beta defensin 2 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. Defensins are thought to fight pathogens by forming pores in the cell wall, 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 a largely analogous protein sequence.

Beta-defensin 2 (BD-2) also known as "skin-antimicrobial peptide 1", SAP1, is a cysteine-rich, human, cationic, antimicrobial peptide originally discovered in lesioned skin. The peptide is encoded by the DEFB4 (defensin beta 4) gene located on chromosome 8 (location: Chr 8: 7.89 - 7.9 Mb).

Beta-defensin 2 (hBD2) is an "antibiotic" peptide expressed by neutrophil granulocytes and numerous epithelia (detected in skin and respiratory tract), which is regulated by inflammatory processes. Together with human beta defensin 3 (hBD3), human beta defensin 2 is one of the most important members of the beta defensin family.

Epithelia are the first to produce beta-defensin 2 upon contact with microorganisms (P. aeruginosa). Beta-Defensin 2 plays a leading role in the surface protection of epithelia. It develops potent antimicrobial activities against Gram-negative bacteria and yeast fungi, but not against Gram-positive S. aureus.

HBD2 and hBD3 influence the viability of Helicobacter pylori. In vitro it could be shown that the expression of human beta defensin 2 was increased up to 40 times the initial value, depending on Helicobacter pylori infection. In vivo, the degree of upregulation correlated with the extent of antrum gastritis. In contrast, the levels of human beta defensin 3 decreased while mRNA remained unchanged. With an eradication of H. pylori the values of human beta defensin 2 normalized (Bauer B et al. 2013).

Keratinocytes in inflammatory skin lesions express locally increased levels of the HBD-2 gene and the encoded protein. Thus, this defensin is massively overexpressed in lesional epidermis of psoriatic patients. This is not detectable in patients with atopic eczema. Serum levels of human beta-defenin-2 are elevated in correlation to the activity and PASI of psoriasis (Abdelmaksood R et al. 2013). This finding is also not detectable in patients with atopic eczema. Serum levels of interferon-gamma and interleukin-10 IFN-gamma, interleukin-17, interleukin-22, TNF-alpha, interleukin-1beta and interleukin-6 go parallel to the increase in defensin. These cytokines enhanced the expression of human defensin-2, whereas IL-10, IL-4 and IL-13 suppress the expression of this peptide (Kanda N et al.2011). Human beta-defensin-2 is a biomarker for psoriasis (Jansen PA et al. 2009).

In UV-irradiated keratinocytes hBD2 is expressed in significantly larger amounts. The hormone-like polypeptide adiponectin is able to suppress this hBD2 overexpression (Kim M et al. 2016).

1. Abdelmaksood R et al (2013) The impact of topical calcipotriol and betamethasone on human beta-defensin 2 expression and serum level in psoriatic patients. Clin Lab 59:277-282.
2. Alp S et al (2005) Expression of beta-defensin 1 and 2 in nasal epithelial cells and alveolar macrophages from HIV-infected patients. Eur J Med Res 10:1-6.
3. Bauer B et al (2013) Differential expression of human beta defensin 2 and 3 in gastric mucosa ofHelicobacter pylori-infected individuals. Helicobacter 18:6-12.
4. Jansen PA et al (2009) Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin. PLoS One 4:e4725.
5. Kanda N et al (2011) Human β-defensin-2 enhances IFN-γ and IL-10 production and suppresses IL-17 production in T cells.J Leukoc Biole 89:935-944.
6. Keskin M et al (2015) Two Cheers for Crohn's Disease and Periodontitis: Beta-Defensin-2 as an Actionable Target to Intervene on Two Clinically Distinct Diseases. OMICS19:443-50.
7. Kim M et al (2016) Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes. PLoS One 11(8):e0161247.
8. Schröder JM et al (1999) Human beta-defensin-2 Int J Biochem Cell Biol 31:645-651.