Pglyrp1

What is PGLYRP1 protein?

PGLYRP1 gene (peptidoglycan recognition protein 1) is a protein coding gene which situated on the long arm of chromosome 19 at locus 19q13. The PGLYRP1 protein is a pattern recognition protein that plays a role in the innate immune system. It is expressed in a variety of cell types, including neutrophils, monocytes, and epithelial cells, and is involved in antimicrobial defense and inflammatory responses in response to bacterial infections. PGLYRP1 is able to directly recognize and bind to the peptidoglycans of bacteria, exert antibacterial effects, and may influence the activation of immune cells through interactions with receptors such as TREM-1. The PGLYRP1 protein is consisted of 196 amino acids and PGLYRP1 molecular weight is approximately 21.7 kDa.

What is the function of PGLYRP1 protein?

The PGLYRP1 protein is a pattern recognition protein that plays a role in innate and acquired immunity. It is mainly expressed in a variety of immune cells, including neutrophils, monocytes, macrophages, and microglia. PGLYRP1 is involved in triggering antimicrobial defense mechanisms, promoting anti-tumor immune responses, and is able to regulate immune responses by interacting with different proteins to form stable protein complexes. PGLYRP1 also interacts with TREM1 (a trigger receptor expressed in myeloid cell 1) to promote neuroinflammation in cultured glial cells via the TREM1-SYk-ERK1/2-STAT3 signaling pathway.

PGLYRP1 related signaling pathway

PGLYRP1, or Peptidoglycan Recognition Protein 1, binds to bacterial peptidoglycans, triggering a cascade that activates the inflammasome and subsequent cytokine release. This interaction not only facilitates direct bacterial killing through lytic activity but also modulates host immune reactions by promoting inflammation and recruitment of immune cells. Dysregulation of this pathway can impair immune defense mechanisms, leading to increased susceptibility to infections. Conversely, overactivation may contribute to excessive inflammation seen in autoimmune diseases.

PGLYRP1 related diseases

PGLYRP1-related diseases encompass a range of conditions primarily associated with compromised immune defenses and increased susceptibility to bacterial infections. This includes recurrent infections, particularly in mucosal surfaces like the respiratory tract and gastrointestinal system, due to PGLYRP1's role in recognizing and eliminating pathogens through peptidoglycan binding and activation of antimicrobial responses. Additionally, dysregulation of PGLYRP1 may contribute to chronic inflammatory diseases by influencing the balance between pro- and anti-inflammatory cytokines, potentially leading to conditions such as inflammatory bowel disease (IBD) or rheumatoid arthritis. Moreover, alterations in PGLYRP1 expression have been implicated in autoimmune disorders and possibly even cancer development, where its antimicrobial properties could impact tumor microenvironment interactions.

Fig1. Tag7 leads to the appearance of cytotoxic lymphocytes after incubation with PBMC. (Tatiana N Sharapova, 2020)

Bioapplications of PGLYRP1

By mimicking the natural function of endogenous PGLYRP1, rhPGLYRP1 binds to bacterial peptidoglycans, facilitating direct microbial killing and modulating immune responses through inflammasome activation. This makes it a promising candidate for therapeutic development against a range of bacterial pathogens, including those resistant to conventional antibiotics. Additionally, its role in regulating inflammation suggests potential applications in managing conditions characterized by dysregulated immune responses, such as inflammatory diseases. Thus, rhPGLYRP1 holds significant promise for advancing treatments in infectious diseases and possibly other inflammatory conditions, leveraging its potent antimicrobial and immunomodulatory properties.

Case Study 1: Alexandra Schnell, 2023

Tumor microenvironmental co-inhibitory molecules impair T cell function, and while immune checkpoint blockade treats cancers effectively, it can cause autoimmune-like side effects. This research indicates that PGLYRP1, highly coexpressed with co-inhibitory genes, could be a valuable target for cancer immunotherapy. Mice lacking Pglyrp1 exhibited reduced tumor growth and enhanced CD8+ T cell activation, suggesting PGLYRP1's inhibitory role. Interestingly, Pglyrp1 deletion also protected against experimental autoimmune encephalomyelitis, suggesting PGLYRP1's proinflammatory role in myeloid cells during autoimmunity.

Fig1. Influence of IL-27 signaling on the expression of Pglyrp1 in vivo.

Fig2. EAE was induced by CFA/MOG. The mean clinical scores of EAE in E8iCrePglyrp1fl/fl

Case Study 2: Anup Bhusal, 2024

PGLYRP1, a pattern-recognition protein involved in antibacterial defense and innate immunity, has an unclear role in neuroinflammation. This study found increased PGLYRP1 expression in inflamed spinal cords and brains of humans and mice, with microglia as the main source. Recombinant PGLYRP1 enhanced gliosis, neuroinflammation, and behavioral changes in animal models. Knocking down Pglyrp1 with shRNA reduced inflammation. Researchers also found TREM1, a myeloid cell receptor, interacts with PGLYRP1, and PGLYRP1 drives neuroinflammation via the TREM1-Syk-Erk1/2-Stat3 pathway in glial cells. These findings suggest microglial PGLYRP1 as a mediator in neuroinflammation and propose it as a potential biomarker and therapeutic target for neuroinflammatory diseases.

Fig3. Western blot analysis revealed the expression of the PGLYRP1 protein in the spinal cords of patients with MS.

Fig4. Disease course of EAE mice after PGLYRP1 protein injection.

Pglyrp1 has several biochemical functions, for example, N-acetylmuramoyl-L-alanine amidase activity,peptidoglycan binding,peptidoglycan receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by Pglyrp1 itself. We selected most functions Pglyrp1 had, and list some proteins which have the same functions with Pglyrp1. You can find most of the proteins on our site.

Pglyrp1 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 Pglyrp1 here. Most of them are supplied by our site. Hope this information will be useful for your research of Pglyrp1.

YWHAZ