DEFB4A

What is DEFB4A Protein?

DEFB4A, or human β-defensin-2, is an antibiotic peptide made by neutrophils and is part of the defensin family. It fights a wide range of microbes, with especially strong action against Gram-negative bacteria. DEFB4A acts under local inflammation, offering antimicrobial effects and binding to CCR6 to attract cells like immature dendritic cells and memory T cells. It's highly expressed in tissues such as the gallbladder and esophagus and could serve as a biomarker in conditions like colds, cystic fibrosis, and lung diseases. DEFB4A also plays a crucial role in immune response regulation and host defense by engaging various signaling pathways in immune and inflammatory processes.

What is the Function of DEFB4A Protein?

DEFB4A, or human β-defensin-2, is a natural antibiotic peptide with impressive antibacterial action, particularly against Gram-negative bacteria. It binds to CC chemokine receptor 6 (CCR6), sparking chemokine activity in CCR6-expressing cells like immature dendritic cells and memory T cells. DEFB4A can also break down Candida albicans' cell membrane by targeting lipid PIP2, leading to the cell's demise. It adjusts local inflammatory responses and acts as a bridge between innate and adaptive immunity. Thus, DEFB4A plays a key role in the body's natural defense, both in fighting bacteria and fine-tuning immune reactions.

DEFB4A Related Signaling Pathway

DEFB4A, known as human β-defensin-2, plays a part in various signaling pathways, especially when it comes to immune responses and inflammation. It interacts with CCR6, waking up cells like immature dendritic ones and memory T cells, thus aiding in chemotaxis. This protein is key during Toll-like receptor activation in monocytes, relying on IL-1 and vitamin D receptors to do its work. DEFB4A is thought to influence antimicrobial peptide actions by blocking the TLR2/1-induced vitamin D pathways. It also upregulates in the NF-κB pathway, involving IκBα phosphorylation, and activates NF-κB binding spots, especially when Haemophilus influenzae is around. These insights show DEFB4A's complex role in managing both innate and adaptive immune responses, especially in terms of antimicrobial and immune modulation.

DEFB4A Related Diseases

The DEFB4A protein, also known as human β-defensin-2, is linked to various diseases, particularly those affecting the respiratory system and immune functions. It's thought to play a key role in central nervous system disorders by either disrupting cell maturation or causing overexpression of inflammatory cytokines. In lung diseases, DEFB4A's expression in lung epithelial cells is crucial and relies on NF-κB and AP-1 protein complexes, plus intracellular calcium. Mutations in DEFB4A genes are closely tied to childhood allergic asthma. Its expression in airway cells, influenced by common asthma treatments like glucocorticoids, can have significant effects. DEFB4A might also serve as a predictor for pneumonia outcomes, as its levels in lung fluids link with C-reactive protein, a sign of its protective role against lung infections. Additionally, DEFB4A helps fight bacterial and fungal infections, with notable activity against Candida albicans. This makes it a potential biomarker for diseases like the common cold, cystic fibrosis, and other lung conditions.

Bioapplications of DEFB4A

DEFB4A, or human β-defensin-2, shows versatile use in biomedical research and industry. It's a natural antibiotic peptide important for immune responses and inflammation. In cancer research, DEFB4A could be a prognostic marker for colorectal cancer; higher levels in tumors often signal a poor outcome. It's closely related to immune regulation, especially in tumor environments, and influences immune suppression, white blood cell functions, and interactions with markers like CD11b and IL17A. DEFB4A's recombinant form is also used in industry, like in EIAab's research products, hinting at industrial potentials. Overall, DEFB4A has wide applications in research, disease markers, immune modulation, and as a therapeutic target, supporting new treatment strategies.

Case Study 1: Chen B. et al. Microb Pathog. 2024

BD2 is a key peptide that helps fight bacterial infections. Scientists looked into how BD2 safeguards against urinary tract infections from E. coli. They conducted experiments using human bladder cells and mice to understand this protective role. Various tests showed that during infection, BD2 levels were low while β-catenin was high. Increasing BD2 improved cell health, reduced inflammation, and restored protein levels in bladder cells. In mice, boosting BD2 also lowered tissue infection and balanced inflammation and protein levels.

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  Fig1. Effect of BD2 overexpression on LPS-induced HCV-29 cell viability was detected by CCK-8 assay.
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  Fig2. Effect of β-catenin knockdown on the expression of tight-junction proteins (ZO-1, Occludin, and Claudin-1), BD2 and β-catenin in LPS-induced HCV-29 cell.

Case Study 2: Kim J. et al. Immunobiology. 2019

Beta-defensins are important in fighting off pathogens like viruses, though their exact roles in immune cells are not fully understood. Researchers had previously found that human β-defensin 2 (HBD 2) can ramp up the body's initial immune response to viral infections and might even assist the adaptive immune system. To dig deeper, they looked at how HBD 2 strengthens antiviral defenses, using the MERS-CoV spike protein's receptor-binding domain as a test subject. Their study revealed that HBD 2 boosts the production of Nod2, type I interferons, and other inflammation-related molecules in THP-1 cells. It also improved activation of specific kinases and regulatory factors more than RBD alone. Additionally, HBD 2-conjugated RBD interacted with CCR2, with Nod2 playing a part in signaling that led to THP-1 cell activation. In essence, HBD 2 supports CCR2-related Nod2 signaling, boosting type I IFNs and inflammatory responses, thus strengthening innate immunity and helping the adaptive immune system respond better to the antigen.

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  Fig3. HBD 2-conjugated S RBD Ag treatment of THP-1 cells stimulates the expression and activation of genes related to Nod2-mediated innate immune signaling.
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  Fig4. THP-1 cells treated with 1 μg/mL HBD 2-conjugated S RBD were subjected to immunofluorescence assay.

DEFB4A has several biochemical functions, for example, . Some of the functions are cooperated with other proteins, some of the functions could acted by DEFB4A itself. We selected most functions DEFB4A had, and list some proteins which have the same functions with DEFB4A. You can find most of the proteins on our site.

Function	Related Protein

DEFB4A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with DEFB4A here. Most of them are supplied by our site. Hope this information will be useful for your research of DEFB4A.