IL24 - interleukin 24 |Elisa - Clia - Antibody - Protein

Background

Interleukin 24 (IL-24) is a cytokine belonging to the IL-10 family, which includes other related cytokines such as IL-10, IL-19, IL-20, IL-22, and IL-26. IL-24 was first identified as melanoma differentiation-associated gene-7 (mda-7), due to its expression being upregulated during the process of melanoma cell differentiation. It plays a key role in immune regulation, cell survival, apoptosis, and the modulation of inflammatory responses. IL-24 is unique in its ability to induce apoptosis selectively in cancer cells without affecting normal cells, making it a promising therapeutic target for cancer treatment.

IL-24 is produced by a variety of immune cells, including macrophages, monocytes, and T-cells, and is involved in both immune modulation and inflammation. Its expression can be triggered by pro-inflammatory signals, such as TNF-α and IFN-γ. IL-24 has also been implicated in tissue repair and has protective functions in certain inflammatory diseases, as it can regulate both inflammatory and anti-apoptotic pathways.

Protein Structure

IL-24 is a monomeric glycoprotein with a length of 206 amino acids and a molecular weight of around 24 kDa. As a member of the IL-10 cytokine family, IL-24 shares structural features common to this group, including the presence of a four-helix bundle fold characteristic of class-II cytokines.

Primary Structure:

• IL-24 is encoded by the IL24 gene located on chromosome 1q32.
• It has a signal peptide at its N-terminus (the first 29 amino acids), followed by the mature cytokine sequence that constitutes its biologically active form.

Secondary and Tertiary Structure:

• IL-24 adopts a four α-helix bundle structure, which is a hallmark of cytokines in the IL-10 family. This structure is critical for its interactions with its receptors and subsequent signaling.
• IL-24 contains multiple disulfide bonds that contribute to its stability and folding.

Quaternary Structure and Receptor Binding:

• IL-24 signals through a heterodimeric receptor complex composed of IL-20 receptor 1 (IL-20R1) and either IL-20 receptor 2 (IL-20R2) or IL-22 receptor 1 (IL-22R1).
• These receptor interactions initiate signaling cascades primarily involving the JAK/STAT pathway, particularly STAT1 and STAT3, which are important for its pro-apoptotic and immune-regulatory functions.

Classification and Subtypes

IL-24 is classified as part of the IL-10 family of cytokines, all of which play roles in immune modulation and share a common receptor usage. IL-24 is closely related to other IL-10 family members, such as IL-19 and IL-20, due to similarities in their receptor usage and functional overlap.

• IL-24 and IL-20 share the use of the IL-20R1/IL-20R2 receptor complex, making them functionally similar in certain aspects of immune regulation.
• IL-24 can also bind the IL-22R1/IL-20R2 receptor complex, which allows it to mediate responses in epithelial tissues, similar to IL-22.

There are no known subtypes of IL-24, but its diverse receptor usage allows it to have varied effects depending on the tissue and cell type where it is expressed.

Function and Biological Significance

IL-24 plays multifaceted roles in regulating immune responses, apoptosis, and inflammation. Its biological activities are primarily mediated through its interaction with specific receptor complexes, leading to the activation of signaling pathways that regulate cell proliferation, differentiation, and survival.

Key Functions:

Induction of Apoptosis:

• One of the most notable functions of IL-24 is its ability to selectively induce apoptosis in tumor cells. This property has garnered significant attention in cancer research, where IL-24 is being studied for its potential as an anticancer therapeutic.
• IL-24 induces apoptosis through various mechanisms, including the generation of reactive oxygen species (ROS), activation of the p38 MAPK pathway, and induction of endoplasmic reticulum (ER) stress. These processes lead to cell death specifically in cancer cells, sparing normal cells.

Immune Modulation:

• IL-24 regulates the immune response by modulating the activity of both innate and adaptive immune cells. It can influence the activity of macrophages, dendritic cells, and T-cells, leading to the secretion of additional cytokines such as TNF-α, IL-6, and IFN-γ.
• By activating the JAK/STAT signaling pathway, IL-24 promotes inflammatory responses while also exerting anti-inflammatory effects depending on the cellular context.

Wound Healing and Tissue Repair:

• IL-24 has a role in tissue repair and wound healing. Its ability to act on epithelial cells and promote cell proliferation and migration contributes to its role in tissue regeneration. In this context, IL-24 can protect tissues from excessive damage during inflammation while promoting the resolution of inflammatory responses.

Inflammatory Response:

• IL-24 is involved in the regulation of inflammatory pathways and can have both pro- and anti-inflammatory effects. This dual functionality depends on the environment and the cells expressing IL-24. For example, in autoimmune diseases like psoriasis and rheumatoid arthritis, IL-24 is often elevated and contributes to chronic inflammation.
• IL-24 can also act in antimicrobial defense by enhancing the production of antimicrobial peptides by epithelial cells, further contributing to host defense mechanisms.

Tumor Suppression:

• IL-24 has gained attention for its ability to suppress tumor growth not only by inducing apoptosis but also by inhibiting angiogenesis (the formation of new blood vessels that supply tumors) and promoting immune surveillance. By activating immune cells in the tumor microenvironment, IL-24 enhances the body's ability to target and eliminate cancer cells.

Clinical Issues

IL-24's broad range of biological activities, including its selective apoptotic effects on tumor cells, has significant clinical implications, particularly in the field of oncology. Its potential as a therapeutic agent for cancer and autoimmune diseases has been explored, with several preclinical and clinical trials investigating its utility in cancer gene therapy.

Diseases and Conditions Associated with IL-24:

Cancer:

• IL-24’s ability to selectively induce apoptosis in cancer cells makes it a promising candidate for cancer gene therapy. Research has focused on delivering the mda-7 gene (which encodes IL-24) to tumor cells using viral vectors, with encouraging results in preclinical models of melanoma, breast cancer, lung cancer, and prostate cancer.
• Clinical trials are underway to determine the efficacy of IL-24-based therapies in treating various forms of cancer. These therapies have shown potential not only in reducing tumor growth but also in enhancing the effects of chemotherapy and radiotherapy.

Autoimmune Diseases:

• Elevated levels of IL-24 have been observed in autoimmune and chronic inflammatory diseases, including psoriasis and rheumatoid arthritis. In psoriasis, IL-24 contributes to the hyperproliferation of keratinocytes and the recruitment of inflammatory cells to the skin, exacerbating disease symptoms.
• Targeting IL-24 or its receptors could provide a novel therapeutic strategy for controlling chronic inflammation in autoimmune diseases.

Inflammatory Conditions:

• Given IL-24’s role in modulating inflammatory responses, dysregulation of its signaling pathways can contribute to a variety of inflammatory conditions, particularly those involving epithelial barriers such as the skin, lungs, and gastrointestinal tract. Therapeutic modulation of IL-24 levels may help manage inflammatory diseases where epithelial damage and immune dysregulation are central to pathology.

Infectious Diseases:

• IL-24’s role in enhancing antimicrobial defenses through the induction of antimicrobial peptides suggests that it may be involved in host defense against bacterial infections, particularly in epithelial tissues. Further research is required to elucidate its role in infectious disease management and potential therapeutic use in enhancing innate immunity.

Summary

IL-24, also known as melanoma differentiation-associated gene-7 (mda-7), is a versatile cytokine with critical roles in apoptosis, immune modulation, and inflammation. Structurally, IL-24 is a member of the IL-10 family, characterized by a four α-helix bundle structure and signaling through receptor complexes shared with IL-20. It selectively induces apoptosis in cancer cells, making it a promising candidate for cancer therapies. IL-24 also modulates immune responses, contributing to both pro- and anti-inflammatory effects depending on the context. Clinically, IL-24’s ability to induce apoptosis in tumor cells, modulate chronic inflammation, and enhance epithelial defenses has significant therapeutic potential in oncology, autoimmune diseases, and infectious diseases. Ongoing research aims to leverage these properties to develop new therapies targeting IL-24 for cancer and other diseases characterized by dysregulated immune responses.