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Event: 1438

Key Event Title

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

Transcription of genes encoding acute phase proteins, Increased

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
Increased transcription of genes encoding APP
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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

Organ 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
Organ term

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; 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
Process Object Action
acute-phase response Acute phase proteins increased

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
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Interaction with lung cells leading to atherosclerosis KeyEvent Ulla Vogel (send email) Under development: Not open for comment. Do not cite Under Development

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
mouse Mus musculus High NCBI
human Homo sapiens 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
Male High
Female 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

Acute phase response is characterized by the change in plasma concentration of acute phase proteins (APP), along with other physiological changes during inflammatory conditions 1,2. In humans, the major APPs are C-reactive protein and serum amyloid A, while in mice the major APPs are serum amyloid A, haptoglobin and serum amyloid P 1,3.

It is widely accepted than APPs are mainly produced by the liver, however several other tissues have been showed to express APPs; these include lungs, intestines, kidneys, skin and adipose tissue in humans 4-7, and kidney, spleen, brain, lung and testis in mice 8,9. According to National Center for Biotechnology Information (NCBI) serum amyloid A isoforms and C-reactive protein genes in mice have been shown to be expressed in tissue from adrenal gland, bladder, central nervous system, colon, duodenum, genital fat pad, heart, kidney, large intestine, limbs, liver, lung, mammary gland, ovary, placenta, small intestine, subcutaneous fat pad, testis and thymus10. In the case of humans, these genes have been shown to be expressed in tissue from adrenal gland, appendix, fat, gall bladder, heart, kidney, liver, lung, placenta, prostate, salivary gland, small intestine, stomach, thymus, thyroid, trachea and uterus10.

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

Gene expression of APPs can be measured from tissue samples using quantitative Polymerase Chain Reaction (PCR). Humans and mice express four SAA isoforms (Saa1, Saa2, Saa3 and Saa4), however Saa3 is a pseudogene in humans11. CRP is expressed in humans and mice, although only moderately expressed in mice12.

It has been shown that in mice the Saa3 isoform is the most differentially expressed APP gene in lung tissue and it is not highly expressed in the liver, while Saa1 gene is the most differentially expressed in liver tissue after exposure to particles 13-15. In humans, it has been shown that crp, saa1, saa2 and saa4 gene expression can be measured in lung samples taken during surgery 16. In addition, microarray analysis can be used to evaluate the gene expression of several APPs at the same time 13.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help
  • Taxonomic applicability: APR is part of the immune reponse and is obseved in vertebrate species3.
  • Life stage applicability: This key event is applicable to all life stages.
  • Sex applicability: This key event is applicable to male and female sexes.


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

1            Gabay, C. & Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340, 448-454, doi:10.1056/NEJM199902113400607 (1999).

2            Mantovani, A. & Garlanda, C. Humoral Innate Immunity and Acute-Phase Proteins. N Engl J Med 388, 439-452, doi:10.1056/NEJMra2206346 (2023).

3            Cray, C., Zaias, J. & Altman, N. H. Acute phase response in animals: a review. Comp Med 59, 517-526 (2009).

4            Schrödl, W. et al. Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine.  10, 1077-1092, doi: (2016).

5            de Dios, O. et al. C-reactive protein expression in adipose tissue of children with acute appendicitis. Pediatr Res 84, 564-567, doi:10.1038/s41390-018-0091-z (2018).

6            Urieli-Shoval, S., Cohen, P., Eisenberg, S. & Matzner, Y. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium. J Histochem Cytochem 46, 1377-1384, doi:10.1177/002215549804601206 (1998).

7            Venteclef, N., Jakobsson, T., Steffensen, K. R. & Treuter, E. Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol Metab 22, 333-343, doi:10.1016/j.tem.2011.04.004 (2011).

8            Kalmovarin, N. et al. Extrahepatic expression of plasma protein genes during inflammation. Inflammation 15, 369-379, doi:10.1007/BF00917353 (1991).

9            Saber, A. T. et al. Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk. PLoS One 8, e69020, doi:10.1371/journal.pone.0069020 (2013).

10          NCBI. <> (2023).

11          Shridas, P. & Tannock, L. R. Role of serum amyloid A in atherosclerosis. Curr Opin Lipidol 30, 320-325, doi:10.1097/MOL.0000000000000616 (2019).

12          Pepys, M. B. & Hirschfield, G. M. C-reactive protein: a critical update. J Clin Invest 111, 1805-1812, doi:10.1172/JCI18921 (2003).

13          Halappanavar, S. et al. Pulmonary response to surface-coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: a toxicogenomic study. Environ Mol Mutagen 52, 425-439, doi:10.1002/em.20639 (2011).

14          Poulsen, S. S. et al. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice. PLoS One 12, e0174167, doi:10.1371/journal.pone.0174167 (2017).

15          Saber, A. T. et al. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease. Wiley Interdiscip Rev Nanomed Nanobiotechnol 6, 517-531, doi:10.1002/wnan.1279 (2014).

16          Calero, C. et al. Differential expression of C-reactive protein and serum amyloid A in different cell types in the lung tissue of chronic obstructive pulmonary disease patients. BMC Pulm Med 14, 95, doi:10.1186/1471-2466-14-95 (2014).