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Event: 1573

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Suppressed MyD88

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Suppressed MyD88

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
macrophage

Organ term

Organ term
immune system

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
Homo sapiens	Homo sapiens	High	NCBI
Mus musculus	Mus musculus	High	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
All life stages	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The initial step in IL-1 signal transduction is a ligand-induced conformational change in the first extracellular domain of the IL-1RI that facilitates recruitment of IL-1RacP (Cavalli, et al. 2015). Through conserved cytosolic regions called Toll- and IL-1R–like (TIR) domains (Radons, et al. 2003), the trimeric complex rapidly assembles two intracellular signaling proteins, myeloid differentiation primary response gene 88 (MYD88) and interleukin-1 receptor–activated protein kinase (IRAK) 4 (Brikos, et al. 2007; Li, et al. 2002). Mice lacking MYD88 or IRAK4 show severe defects in IL-1 signaling (Adachi, et al. 1998; Medzhitov, et al. 1998; Suzuki, et al. 2002). Similarly, humans with mutations in the IRAK4 gene have defects in IL-1RI and Toll-like receptor (TLR) signaling (Picard, et al. 2003). IL-1, IL-1RI, IL-RAcP, MYD88, and IRAK4 form a stable IL-1–induced first signaling module (Brikos, et al. 2007). Moreover, patients with defects in MyD88 gene have an increased susceptibility to pyogenic bacterial infections (Picard, et al. 2010; von Bernuth, et al. 2008). Similarly, MyD88 knockout mice showed fatal mycobacterium tuberculosis infection (Picard, et al. 2010; Scanga, et al. 2004).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

The suppressed MyD88 cannnot be measured. Therefore, instead of measuring the suppressed MyD88 signaling, the inhibition can be measured by d quantitating ownstream event, such as phosphorylated NF-kB or the proteins or mRNA of IL-6 , IL-8 or other IL-1–responsive cytokines or COX-2 produced by IL-1 stimulated macrophages or macrophage cell lines in the presence of inhibitors (Ref).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

The Myd88 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, mosquito, and frog. https://www.ncbi.nlm.nih.gov/homologene?Db=homologene&Cmd=Retrieve&list_uids=1849

Following either vaccination in adult humans or virus challenge in adult rats, the expression of TLR-pathway and pro-inflammatory genes (for example, TLR7, myeloid differentiation primary response gene 88 (MYD88), retinoic acid inducible gene-I (RIGI), IRF7, IFNB, Janus kinase 2 (JAK2), signal transducer and activator of transcription (STAT3), nuclear factor-κB (NFKB), IFNG and tumour necrosis factor (TNF)) is higher in female than male PBMCs from humans and tissues from rats (Hannah, et al. 2008; Klein, et al. 2010).

References

List of the literature that was cited for this KE description. More help