1. Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response
Martyna Cieślik, Natalia Bagińska, Andrzej Górski, Ewa Jończyk-Matysiak Cells. 2021 Nov 3;10(11):2991. doi: 10.3390/cells10112991.
Studies described so far suggest that human β-defensin 2 is an important protein of innate immune response which provides protection for the human organism against invading pathogens of bacterial, viral, fungal, as well as parasitical origin. Its pivotal role in enhancing immunity was proved in infants. It may also be considered a marker of inflammation. Its therapeutic administration has been suggested for maintenance of the balance of systemic homeostasis based on the appropriate composition of the microbiota. It has been suggested that it may be an important therapeutic tool for modulating the response of the immune system in many inflammatory diseases, offering new treatment modalities. For this reason, its properties and role in the human body discussed in this review should be studied in more detail.
2. Human beta-defensin-2
J M Schröder, J Harder Int J Biochem Cell Biol. 1999 Jun;31(6):645-51. doi: 10.1016/s1357-2725(99)00013-8.
Human beta-defensin-2 (HBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide recently discovered in psoriatic lesional skin. It is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive Staphylococcus aureus. HBD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as Pseudomonas aeruginosa or cytokines such as TNF-alpha and IL-1 beta. The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions such as psoriasis as well as in the infected lung epithelia of patients with cystic fibrosis. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare.
3. Human β-Defensin 2 (HBD-2) Displays Oncolytic Activity but Does Not Affect Tumour Cell Migration
Guneet K Bindra, Scott A Williams, Fung T Lay, Amy A Baxter, Ivan K H Poon, Mark D Hulett, Thanh Kha Phan Biomolecules. 2022 Feb 6;12(2):264. doi: 10.3390/biom12020264.
Defensins form an integral part of the cationic host defence peptide (HDP) family, a key component of innate immunity. Apart from their antimicrobial and immunomodulatory activities, many HDPs exert multifaceted effects on tumour cells, notably direct oncolysis and/or inhibition of tumour cell migration. Therefore, HDPs have been explored as promising anticancer therapeutics. Human β-defensin 2 (HBD-2) represents a prominent member of human HDPs, being well-characterised for its potent pathogen-killing, wound-healing, cytokine-inducing and leukocyte-chemoattracting functions. However, its anticancer effects remain largely unknown. Recently, we demonstrated that HBD-2 binds strongly to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a key mediator of defensin-induced cell death and an instructional messenger during cell migration. Hence, in this study, we sought to investigate the lytic and anti-migratory effects of HBD-2 on tumour cells. Using various cell biological assays and confocal microscopy, we showed that HBD-2 killed tumour cells via acute lytic cell death rather than apoptosis. In addition, our data suggested that, despite the reported PI(4,5)P2 interaction, HBD-2 does not affect cytoskeletal-dependent tumour cell migration. Together, our findings provide further insights into defensin biology and informs future defensin-based drug development.
