IL-1 is also a mediator of the acute inflammatory response and has many actions similar to those of TNF. A major cellular source of IL-1, like that of TNF, is activated mononuclear phagocytes. IL-1 is also produced by many cell types other than macrophages, such as neutrophils, DCs, epithelial cells (e.g., keratinocytes), and endothelial cells. There are two forms of IL-1, called IL-1α and IL-1β, which are less than 30% homologous, but they bind to the same cell surface receptors and have the same biologic activities. The main biologically active secreted form in the setting of infections and most immune responses is IL-1β.

IL-1 production usually requires two distinct signals: one that activates new gene transcription and production of a 33-kD precursor pro–IL-1β polypeptide and a second that activates the inflammasome to proteolytically cleave the pre cursor to generate the 17-kD mature IL-1β protein (see Fig. 1). As discussed earlier in this chapter, IL-1β gene transcription is induced by TLR, NLR, and RLR signaling pathways that activate NF-κB, whereas pro–IL-1β cleavage is mediated by caspase-1, which is activated by inflammasomes. TNF can also stimulate phagocytes and other cell types to produce IL-1. This is an example of a cascade of cytokines that have simi lar biologic activities. Unlike most secreted proteins, neither IL-1α nor IL-1β has a hydrophobic signal sequence to target the nascent polypeptide to the endoplasmic reticulum mem brane. As discussed earlier, IL-1β may be secreted through membrane pores formed by gasdermin D and/or released from cells dying by pyroptosis.

Fig1. The stimulator of interferon (IFN) genes (STING) cytosolic DNA sensing pathway. Cytoplasmic microbial DNA and self DNA that accumulates in the cytosol activate the enzyme cyclic guanosine mono phosphate–adenosine monophosphate (GMP-AMP) synthase (cGAS), which catalyzes the synthesis of cyclic GMP-AMP (cGAMP) from adenosine triphosphate (ATP) and guanosine triphosphate (GTP). cGAMP binds to STING in the endoplasmic reticulum (ER) membrane, causing STING to translocate to the Golgi (not shown), and then STING recruits and activates the kinase TANK-binding kinase 1 (TBK1), which phosphorylates interferon regulatory factor 3 (IRF3) and IRF7. Phospo-IRF3 and -7 move to the nucleus, where they induce type I IFN gene expression. Self DNA in the cytosol may be produced as a result of genomic or mitochondrial dam age. The bacterial second messenger molecules cyclic di-GMP (c-di-GMP) and cyclic di-AMP (c-di-AMP) are directly sensed by STING. NF-κB, Nuclear factor kappa B.

IL-1 mediates its biologic effects through a membrane receptor called the type I IL-1 receptor, which is expressed on many cell types, including endothelial cells, epithelial cells, and leukocytes. This receptor is an integral membrane protein that contains an extracellular ligand-binding Ig domain and a TIR signaling domain in the cytosolic region, which we described earlier in reference to TLRs. The signaling events that occur when IL-1 binds to the type I IL-1 receptor are similar to those triggered by TLRs and result in the activation of NF-κB and AP-1 transcription fac tors. A second IL-1 receptor, called the type II IL-1 receptor, appears incapable of activating downstream signals, and serves as a decoy receptor that limits responses to IL-1.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الخدمية ينفذ حملة لتنظيف الشوارع المحيطة بصحن مرقد أبي الفضل العباس (عليه السلام)

وفد العتبة العباسية المقدسة يزور شعبة الإعداد البدني للاطّلاع على برنامج تأهيل المنتسبين الجدد

قسم بين الحرمين يقدم جهودًا مضاعفة لإعادة المفقودات إلى الزائرين

بعد برامج تدريبية متخصصة.. متحف الكفيل يبيّن منجزات ملاكاته في فن الخاتم (الأرابيسك)

المزيد

الآخبار الصحية

ماذا يحدث إذا تناولنا الطعام مرة واحدة فقط في اليوم

اكتشاف عوامل خطر غير متوقعة لمرض الكبد الدهني

فيروس هانتا والسفينة الموبوءة.. تحديث من الصحة العالمية

طبيب يحسم الجدل السجائر الإلكترونية وعلاقتها بالسرطان

المزيد

الآخبار التكنلوجية

لأول مرة في الولايات المتحدة.. تشغيل مفاعل مصغر نووي يغذي الذكاء الاصطناعي بالطاقة

الكشف عن تفاصيل أول عملية ناجحة لاستعادة انتاج الحيوانات المنوية

أطلس يكشف خفايا الجسم البشري بدقة أرفع بـ50 مرة من شعر الإنسان

المتحف المصري الكبير يتحول إلى "أيقونة خضراء" بدعم ياباني

المزيد

مواضيع ذات صلة

Double Antibody Sandwich ELISA (DAS ELISA)

Enzyme Immunosorbent Assays

Antibody Structure and Function

Apoptosis in the Immune System

The Major Proinflammatory Cytokines of Innate Immunity: Interleukin-6

The Major Proinflammatory Cytokines of Innate Immunity: Tumor Necrosis Factor

The Immune Receptor Family

Collectins and Ficolins

Soluble Effector Molecules of Innate Immunity: Pentraxins

Soluble Effector Molecules of Innate Immunity : The Complement System

MHC Genes

Cytokine-Producing Innate Lymphoid Cells