This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
Event: 1438
Key Event Title
Transcription of genes encoding acute phase proteins, Increased
Short name
Biological Context
Level of Biological Organization |
---|
Organ |
Organ term
Organ term |
---|
lung |
Key Event Components
Process | Object | Action |
---|---|---|
acute-phase response | Acute phase proteins | increased |
Key Event Overview
AOPs Including This Key Event
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 Do not cite | Under Development |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
Life Stages
Life stage | Evidence |
---|---|
All life stages | High |
Sex Applicability
Term | Evidence |
---|---|
Male | High |
Female | High |
Key Event Description
Acute phase proteins (APPs) are proteins that have an increase in plasma concentration of at least 25% during an acute phase response (Gabay & Kushner, 1999; Mantovani & Garlanda, 2023). In humans, the major APPs are C reactive protein (CRP) and serum amyloid A (SAA), while in mice the major APPs are SAA, haptoglobin and serum amyloid P (Cray, Zaias, & Altman, 2009; Gabay & Kushner, 1999).
It is widely accepted than APPs are mainly produced in the liver, while several other tissues have been shown to express APPs. In humans, APP genes have been shown to be expressed in the adrenal gland, adipose tissue, appendix, gall bladder, heart, kidney, liver, lung, placenta, prostate, salivary gland, skin, small intestine, stomach, thymus, thyroid, trachea and uterus (de Dios et al., 2018; NCBI, 2023; Schrödl et al., 2016; Urieli-Shoval, Cohen, Eisenberg, & Matzner, 1998; Venteclef, Jakobsson, Steffensen, & Treuter, 2011). In mice, APPs have been shown to be expressed in the adrenal gland, bladder, central nervous system, colon, duodenum, genital fat pad, heart, kidney, large intestine, limbs, liver, lung, mammary gland, ovary, placenta, small intestine, spleen, subcutaneous fat pad, testis and thymus (Kalmovarin et al., 1991; NCBI, 2023; Saber et al., 2013).
Table 1 presents a list of acute phase response genes in humans and mice according the National Center for Biotechnology Information (NCBI): Table 1.
It is important to note that humans and mice express four SAA isoforms (Saa1, Saa2, Saa3 and Saa4), while Saa3 is a pseudogene in humans (Shridas & Tannock, 2019). CRP is expressed in humans and mice, although only moderately expressed in mice (Pepys & Hirschfield, 2003).
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 (Halappanavar et al., 2011; Poulsen et al., 2017; Saber et al., 2014).
How It Is Measured or Detected
Gene expression of acute phase proteins (APPs) can be measured from tissue samples using quantitative Polymerase Chain Reaction (PCR). This technique allows the amplification of selected fragments of DNA or cDNA by using primers (i.e. known end-portions of the selected DNA). By repeated cycles of transcription, DNA is amplified. The use of fluorescent probes to quantify the expression the targeted DNA, as the binding of the probe to this DNA emits a fluorescent signal. Sequences of RNA can be quantify using PCR, by first synthetizing DNA from a RNA sample, resulting in cDNA. This technique is called reverse transcriptase PCR (Nelson, Nelson, Lehninger, & Cox, 2017).
Other techniques for evaluating the expression of several APPs at the same time are microarray analysis and total RNA sequencing (Halappanavar et al., 2011; Nelson et al., 2017).
To evaluate this key event in mice, gene expression of Saa3 can be quantified in lung tissue and Saa1 gene in liver tissue after exposure to a stressor (Halappanavar et al., 2011; Poulsen et al., 2017; Saber et al., 2014).
In humans, it is not common to measure gene expression as a tissue sample is required, however gene expression of crp, saa1, saa2 and saa4 can be measured from samples taken during surgery (Calero et al., 2014).
Domain of Applicability
- Taxonomic applicability: Acute phase response is part of the immune response and is observed in vertebrate species (Cray et al., 2009).
- Life stage applicability: This key event is applicable to all life stages.
- Sex applicability: This key event is applicable to male and female sexes.
References
Calero, C., Arellano, E., Lopez-Villalobos, J. L., Sanchez-Lopez, V., Moreno-Mata, N., & Lopez-Campos, J. L. (2014). 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
Cray, C., Zaias, J., & Altman, N. H. (2009). Acute phase response in animals: a review. Comp Med, 59(6), 517-526.
de Dios, O., Gavela-Perez, T., Aguado-Roncero, P., Perez-Tejerizo, G., Ricote, M., Gonzalez, N., . . . Soriano-Guillen, L. (2018). C-reactive protein expression in adipose tissue of children with acute appendicitis. Pediatr Res, 84(4), 564-567. doi:10.1038/s41390-018-0091-z
Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. N Engl J Med, 340(6), 448-454. doi:10.1056/NEJM199902113400607
Halappanavar, S., Jackson, P., Williams, A., Jensen, K. A., Hougaard, K. S., Vogel, U., . . . Wallin, H. (2011). 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(6), 425-439. doi:10.1002/em.20639
Kalmovarin, N., Friedrichs, W. E., O'Brien, H. V., Linehan, L. A., Bowman, B. H., & Yang, F. (1991). Extrahepatic expression of plasma protein genes during inflammation. Inflammation, 15(5), 369-379. doi:10.1007/BF00917353
Mantovani, A., & Garlanda, C. (2023). Humoral Innate Immunity and Acute-Phase Proteins. N Engl J Med, 388(5), 439-452. doi:10.1056/NEJMra2206346
NCBI. (2023). Retrieved from https://www.ncbi.nlm.nih.gov/gene
Nelson, D. L., Nelson, D. L., Lehninger, A. L., & Cox, M. M. (2017). Lehninger Principles of biochemistry (Seventh edition ed.). Macmillan Higher Education: Basingstoke.
Pepys, M. B., & Hirschfield, G. M. (2003). C-reactive protein: a critical update. J Clin Invest, 111(12), 1805-1812. doi:10.1172/JCI18921
Poulsen, S. S., Knudsen, K. B., Jackson, P., Weydahl, I. E., Saber, A. T., Wallin, H., & Vogel, U. (2017). Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice. PLoS One, 12(4), e0174167. doi:10.1371/journal.pone.0174167
Saber, A. T., Jacobsen, N. R., Jackson, P., Poulsen, S. S., Kyjovska, Z. O., Halappanavar, S., . . . Vogel, U. (2014). Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 6(6), 517-531. doi:10.1002/wnan.1279
Saber, A. T., Lamson, J. S., Jacobsen, N. R., Ravn-Haren, G., Hougaard, K. S., Nyendi, A. N., . . . Vogel, U. (2013). Particle-induced pulmonary acute phase response correlates with neutrophil influx linking inhaled particles and cardiovascular risk. PLoS One, 8(7), e69020. doi:10.1371/journal.pone.0069020
Schrödl, W., Büchler, R., Wendler, S., Reinhold, P., Muckova, P., Reindl, J., & Rhode, H. (2016). Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine. 10(11), 1077-1092. doi:https://doi.org/10.1002/prca.201600028
Shridas, P., & Tannock, L. R. (2019). Role of serum amyloid A in atherosclerosis. Curr Opin Lipidol, 30(4), 320-325. doi:10.1097/MOL.0000000000000616
Urieli-Shoval, S., Cohen, P., Eisenberg, S., & Matzner, Y. (1998). Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium. J Histochem Cytochem, 46(12), 1377-1384. doi:10.1177/002215549804601206
Venteclef, N., Jakobsson, T., Steffensen, K. R., & Treuter, E. (2011). Metabolic nuclear receptor signaling and the inflammatory acute phase response. Trends Endocrinol Metab, 22(8), 333-343. doi:10.1016/j.tem.2011.04.004