Abstract

Interferon regulatory factor 8 (IRF-8) is a transcription suppressor that functions through associations with other transcription factors, contributing to the growth and differentiation of bone marrow cells and the activation of macrophages. IRF-8 expression profoundly affects pathogenic processes ranging from infections to blood diseases. Interleukin-9 (IL-9) is a multipotent cytokine that acts on a variety of immune cells by binding to the IL-9 receptor (IL-9R) and is involved in a variety of diseases such as cancer, autoimmune diseases, and other pathogen-mediated immune regulatory diseases. Studies have shown that IL-9 levels are significantly increased in the serum of patients with diffuse large B-cell lymphoma (DLBCL), and IL-9 levels are correlated with the DLBCL prognostic index. The activator protein-1 (AP-1) complex is a dimeric transcription factor that plays a critical role in cellular proliferation, apoptosis, angiogenesis, oncogene-induced transformation, and invasion by controlling basic and induced transcription of several genes containing the AP-1 locus. The AP-1 complex is involved in many cancers, including hematological tumors. In this report, we systematically review the precise roles of IL-9, IRF-8, and AP-1 in tumor development, particularly with regard to DLBCL. Finally, the recent progress in IRF-8 and IL-9 research is presented; the possible relationship among IRF-8, IL-9, and AP-1 family members is analyzed; and future research prospects are discussed.

Highlights

  • Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, and it was defined as a diffuse growth of neoplastic large B lymphoid cells with a nuclear size equal to or exceeding normal macrophage nuclei by the World Health Organization

  • IRF-8PU.1 participates in IFN-stimulated response elements (ISREs)-mediated transcription, enhancing the transcription induced by IFN-stimulated gene factor 3 (ISGF3) in macrophages, which contribute to viral infection resistance by producing ISG family proteins [93]

  • Activator protein-1 (AP-1) complex activation is marked by constitutive activation of the transcription factor nuclear factor-kB (NF-kB), which controls the expression of genes promoting cell survival and proliferation [90]

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Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults, and it was defined as a diffuse growth of neoplastic large B lymphoid cells with a nuclear size equal to or exceeding normal macrophage nuclei by the World Health Organization. The transcription factor PU.1 is one of the proteins that directly interacts with IRF-8, which regulates the expression levels of various myeloidspecific genes [16]. IL-9 was initially described as a growth factor secreted by activated helper T cells type 2 (Th2), which exerts the effects through the members of the gc family of cytokines on target cells, affects various immune cells through IL-9R, and plays different functions in immune and inflammatory responses [44,45,46].

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