白介素1信号通路图
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The Interleukin 1 family is a group of 11 beta trefoil cytokine s.
They play a central role in the regulation of immune and inflammatory responses.
The history of discovery of these cytokines begins with studies on the pathogenesis of fever. The studies were performed by Menkin and Beeson in 1943-1948 on the fever producing properties of proteins released from rabbit peritoneal exudate Cell s. These studies were followed by contributions of several investigators, who were primarily interested in the link between fever and infection/inflammation. The basis for the term "interleukin" was to streamline the growing number of biological properties attributed to soluble factors from macrophages and lymphocytes. IL-1 was the name given to the macrophage product, whereas IL-2 was used to define the lymphocyte product. At the time of the assignment of these names, there was no amino acid sequence analysis known and the terms were used to define biological properties. In 1985 two distinct, but distantly related complementary DNAs encoding proteins sharing human IL-1 activity were reported to be isolated from a macrophage cDNA library, thus defining two individual members of the IL-1 family - IL-1α and IL-1β.
<center> </center> The family of TLRs and pro-inflammatory signal-transduction pathways that recruit NFκ B. The extraCell ular domains of Toll-like receptors (TLRs) include multiple leucine-rich repeats; TLR cytoplasmic domains are similar to the cytoplasmic portion of the interleukin 1 (IL-1) receptor (IL-1R). TLR2 recognizes the pathogen-associated molecular patterns that are produced by Gram-positive (Gram+) bacterial cell wall components. TLR4, in association with CD14 and a molecule known as MD-2, is crucial for the recognition of lipopolysaccharide (LPS) from Gram-negative (Gram–) bacteria. Flagellin, the principal element of bacterial flagella, is a highly virulent molecule that is recognized by TLR5. TLR9 is required for the inflammatory response that is triggered by bacterial DNA. TLR3 engages the innate immune response in the presence of viruses that produce double-stranded RNA (dsRNA). The broad spectrum of components recognized by these receptors indicates that TLRs form heteromeric complexes. The cytoplasmic domain of TLR2 can form functional pairs with TLR6 and TLR1, leading to signal transduction and cytokine gene expression. All TLRs activate signalling pathways that are similar to those activated by IL-1, because they share a Toll/IL-1R homology domain that can interact with the adaptor protein MyD88. p50 and p65 are the two most common DNA-binding subunits of the nuclear factor κ B (NFκ B) dimer, and have the ability to trigger the transcription of target genes that encode cytokine s, chemokines, proteins of the complement system, enzymes, adhesion molecules, immune receptors and others. See main text for details of the kinases involved in the NFκ B nuclear translocation. ACP1, accessory protein 1; IKAP, Iκ B kinase complex (IKK-α β γ )-associated protein; Iκ B, inhibitor of NFκ B; IRAK, IL-1R-associated kinase; LTA, lipoteichoic acid; NIK, NFκ B-inducing kinase; PGN, peptidoglycan; RIP, receptor-interacting protein; TNF, tumour necrosis factor; TNFR, TNF receptor; TRADD, TNFR1-associated protein with death domain; TRAF, TNFR-associated factor; Ub, ubiquitin.
