Resistin-like molecule beta (RELM-β), also known as FIZZ2, is a member of the resistin-like molecule family, which includes Resistin (FIZZ3), RELM-α (FIZZ1), and RELM-γ (FIZZ4). RELM-β is particularly notable for its presence in rodents, where it plays significant roles in various physiological processes, including antimicrobial defense and tissue remodeling.
RELM-β is a secreted protein with a molecular mass of approximately 18.0 kDa, consisting of two identical 83 amino acid polypeptide chains linked by a single disulfide bond . It is produced by goblet cells in the intestine and has been implicated in several biological processes:
Antimicrobial Activity: RELM-β exhibits bactericidal activity, particularly against Gram-negative bacteria, by forming size-selective pores that permeabilize bacterial membranes .
Tissue Remodeling: It promotes fibroblast proliferation and differentiation, contributing to airway remodeling and inflammation .
RELM-β has been shown to selectively kill Gram-negative bacteria, such as Pseudomonas aeruginosa and Citrobacter rodentium, while having less pronounced effects on Gram-positive bacteria like Listeria monocytogenes and Enterococcus faecalis . This specificity is crucial for maintaining the balance of gut microbiota.
In wild mice, RELM-β expression is significantly increased in response to intestinal helminth infections, suggesting a role in immune defense against parasitic infections . This upregulation is independent of the presence of other pathogens like Eimeria spp.
RELM-β is involved in driving spontaneous colitis in certain mouse models by depleting protective commensal microbes . Additionally, it contributes to airway remodeling and inflammation by promoting fibroblast proliferation .
Q: How can I design an experiment to study RELM-β expression in mice, particularly in the context of helminth infections? A: To study RELM-β expression, you can use a combination of molecular biology techniques such as PCR for gene expression analysis and ELISA for protein quantification. For helminth infections, collect fecal pellets from infected mice and analyze RELM-β levels using techniques like those described in . Include controls without helminths to compare expression levels.
Q: What statistical methods should I use to analyze RELM-β expression data in the presence of helminths and other pathogens like Eimeria? A: Use statistical models that account for multiple predictors, such as linear regression or generalized linear models. Include variables like helminth species richness and Eimeria load. Compare models using the Akaike information criterion (AIC) to determine the best fit, as shown in .
Q: How does RELM-β contribute to intestinal inflammation in mouse models? A: RELM-β promotes IFN-γ-driven intestinal inflammation by acting on macrophages. It also has a direct effect on worm chemotaxis, which can influence the expulsion of helminths .
Q: Does RELM-β have bactericidal properties, and if so, how does it affect Gram-negative bacteria? A: Yes, RELM-β is a bactericidal protein that selectively kills Gram-negative bacteria by forming pores in bacterial membranes. This is demonstrated in studies where mice lacking RELM-β showed increased susceptibility to such infections .
Q: Which cells are responsible for the constitutive expression of RELM-β in the mouse colon? A: RELM-β is constitutively expressed by goblet cells and enterocytes in the colon, playing a role in maintaining colonic homeostasis .
Q: How does RELM-β contribute to the expulsion of helminths in mouse models? A: RELM-β directly affects worm survival and fecundity, potentially expelling helminths through its action on the parasites rather than indirect host-mediated mechanisms .
Q: What are the differences in function between RELM-β and RELM-α in mouse models of infection? A: RELM-β promotes IFN-γ-driven inflammation and affects worm chemotaxis, whereas RELM-α limits Th2 responses in worm-infected mice. RELM-α does not have the same effect on worm survival as RELM-β .
Q: What methods are recommended for detecting RELM-β in mouse fecal samples? A: Use ELISA kits specifically designed for mouse RELM-β detection. Homogenize fecal pellets in PBS, centrifuge, and use the supernatant for ELISA analysis without dilution, as described in .
Q: How can I address potential contradictions in RELM-β expression data across different studies? A: Consider factors like differences in experimental design, helminth species used, and the presence of co-infections. Use statistical models to control for these variables and assess their impact on RELM-β expression .
Q: What are some potential future research directions for studying RELM-β in mouse models? A: Investigate RELM-β's role in other types of infections, explore its potential as a biomarker for gut barrier integrity, and examine its interactions with other immune molecules to better understand its function in maintaining gut homeostasis .
Helminth Species | RELM-β Expression (Fold Change) | Eimeria Presence |
---|---|---|
H. polygyrus | 3.2 ± 0.5 | Yes |
T. muris | 2.8 ± 0.3 | No |
Control | 1.0 ± 0.2 | No |
This table illustrates how RELM-β expression can vary with different helminth species and the presence of Eimeria co-infections.
Helminth Infections and RELM-β: Studies have shown that RELM-β expression increases significantly in the presence of helminths, suggesting its role as a marker for helminth infections .
RELM-β and Bacterial Infections: RELM-β has been identified as a bactericidal protein effective against Gram-negative bacteria, highlighting its broader role in innate immunity .
Cellular Expression: RELM-β is constitutively expressed by goblet cells and enterocytes in the mouse colon, contributing to colonic homeostasis .
RELM-β is a non-glycosylated protein consisting of 83 amino acids, with a molecular weight of approximately 8.9 kDa . It is expressed primarily in the colon and small intestine . The protein is secreted by intestinal goblet cells and its secretion is induced by Th2 cytokines in response to nematode infections .
RELM-β plays a significant role in the immune response, particularly in the context of parasitic infections. It is involved in the regulation of inflammation and has been shown to be upregulated in various inflammatory conditions . The protein’s function is closely related to its ability to form homodimers, which are essential for its biological activity .
Recombinant mouse RELM-β is typically produced in Escherichia coli and is available as a sterile filtered, lyophilized powder . The recombinant protein is often used in research to study its role in inflammation and immune response. It is important to handle the reconstituted protein with care, ensuring it is aliquoted and stored at -20°C to maintain its stability .