Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkB alpha, NFKBIA, or IKBA), is a member of the NF-kappa-B inhibitor family that function to inhibit the NF-kB transcription factor. NFKBIA inhibits NF-kB by masking the nuclear localization signals (NLS) of NF-kB proteins and keeping them sequestered in an inactive state in the cytoplasm. In addition, NFKBIA blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-kB's proper functioning. Signal-induced degradation of I kappa B alpha exposes the nuclear localization signal of NF-kappa B, thus allowing it to translocate into the nucleus and activate transcription from responsive genes. An autoregulatory loop is established when NF-kappa B induces expression of the I kappa B alpha gene and newly synthesized I kappa B alpha accumulates in the nucleus where it negatively regulates NF-kappa B-dependent transcription. As part of this post-induction repression, the nuclear export signal on I kappa B alpha mediates transport of NF-kappa B-I kappa B alpha complexes from the nucleus to the cytoplasm. Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival. Polymorphisms in NFKBIA may be important in pre-disposition to and outcome after treatment, of multiple myeloma (MM). The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell lymphoproliferative diseases.
IL-10 is a anti-inflammatory cytokine which belongs to the IL-10 family. It is produced by a variety of cell lines, including T-cells, macrophages, mast cells and other cell types, while it is produced primarily by monocytes and to a lesser extent by lymphocytes. IL-10 is mainly expressed in monocytes and Type 2 T helper cells (TH2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain subset of activated T cells and B cells. IL-10 has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. The importance of interleukin 10 for counteracting excessive immunity in the human body is revealed by the fact that patients with Crohn's disease react favorably towards treatment with bacteria producing recombinant IL-10. IL-10 inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. It also displays a potent ability to suppress the antigen-presentation capacity of antigen presenting cells. However, it is also stimulatory towards certain T cells and mast cells and stimulates B cell maturation and antibody production.
Interleukin 10(IL10), also known as cytokine synthesis inhibitory factor (CSIF),is a secreted protein and belongs to the IL-10 family. IL-10 is secreted by many activated hematopoietic cell types as well as hepatic stellate cells, keratinocytes, and placental cytotrophoblasts . IL-10 is an anti-inflammatory TH2 cytokine that has a critical role in limiting the immune response to pathogens to prevent host damage. As IL-10 in produced in several T helper populations, it is proposed that it provides a feedback loop to limit the effector functions of macrophages and DCs on T cells. Once expressed, IL-10 signals through the IL-10 receptor (IL-10R) to activate STAT3. As IL-10 is a strong inhibitor of inflammation, it has become a viable biomarker for various diseases and conditions as well as a therapeutic molecule for certain conditions. In addition to elevated levels in parasitic infection, high expression levels of IL-10 are also found in retroviral infections inducing immunodeficiency. The immunosuppressive properties of IL-10 suggest a possible clinical use of IL-10 in suppressing rejections of grafts after organ transplantations.
Interleukin (IL)-10 is an anti-inflammatory cytokine, produced by T helper (Th) cells, macrophages, monocytes, and B cells, that plays a crucial role in preventing inflammatory and autoimmune pathologies. It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. IL-10 can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway. IL-10, along with its receptors, describes an important role in pathogenesis of various diseases, including infectious, inflammatory, autoimmune diseases. IL-10 mutations are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis.
Inserisci la tua e-mail e seleziona le aree di interesse per ricevere le ultime novità, approfondimenti e promozioni.
Seleziona uno o più ambiti di interesse per ricevere comunicazioni più utili e mirate.
2025 TEMA Ricerca - All Rights Reserved.
