Regulation of serum amyloid A protein expression during the acute-phase response

The acute-phase (AP) serum amyloid A proteins (A-SAA) are multifunctional apolipoproteins which are involved in cholesterol transport and metabolism, and in modulating numerous immunological responses during inflammation and the AP response to infection, trauma or stress. During the AP response the hepatic biosynthesis of A-SAA is up-regulated by pro-inflammatory cytokines, and circulating concentrations can increase by up to 1000-fold. Chronically elevated A-SAA concentrations are a prerequisite for the pathogenesis of secondary amyloidosis, a progressive and fatal disease characterized by the deposition in major organs of insoluble plaques composed principally of proteolytically cleaved A-SAA, and may also contribute to physiological processes that lead to atherosclerosis. There is therefore a requirement for both positive and negative control mechanisms that permit the rapid induction of A-SAA expression until it has fulfilled its host-protective function(s) and subsequently ensure that its expression can be rapidly returned to baseline. These mechanisms include modulation of promoter activity involving, for example, the inducer nuclear factor κB (NF-κB) and its inhibitor IκB, up-regulatory transcription factors of the nuclear factor for interleukin-6 (NF-IL6) family and transcriptional repressors such as yin and yang 1 (YY1). Post-transcriptional modulation involving changes in mRNA stability and translation efficiency permit further up- and down-regulatory control of A-SAA protein synthesis to be achieved. In the later stages of the AP response, A-SAA expression is effectively down-regulated via the increased production of cytokine antagonists such as the interleukin-1 receptor antagonist (IL-1Ra) and of soluble cytokine receptors, resulting in less signal transduction driven by pro-inflammatory cytokines.

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Differential transcription of the mouse acute phase serum amyloid A genes in response to pro-inflammatory cytokines

Amyloid ◽

10.3109/13506120209114098 ◽

2002 ◽

Vol 9 (4) ◽

pp. 229-236 ◽

Cited By ~ 22

Author(s):

Caroline F. Thorn ◽

Alexander S. Whitehead

Keyword(s):

Inflammatory Cytokines ◽

Acute Phase ◽

Serum Amyloid A ◽

Serum Amyloid ◽

Amyloid A ◽

Differential Transcription ◽

Acute Phase Serum ◽

Pro Inflammatory Cytokines

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Expression of serum amyloid A protein in the absence of the acute phase response does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)32143-x ◽

1999 ◽

Vol 40 (4) ◽

pp. 648-653 ◽

Cited By ~ 7

Author(s):

Hiroshi Hosoai ◽

Nancy R. Webb ◽

Jane M. Glick ◽

Uwe J.F. Tietge ◽

Matthew S. Purdom ◽

...

Keyword(s):

Transgenic Mice ◽

Acute Phase ◽

Acute Phase Response ◽

Serum Amyloid A ◽

Hdl Cholesterol ◽

Phase Response ◽

Serum Amyloid ◽

Amyloid A ◽

Serum Amyloid A Protein

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Acute Phase Proteins (Haptoglobin and Serum Amyloid A) and Pro-Inflammatory Cytokines (IL-12 and IL-10) in Cows Vaccinated with Prototype Killed S. aureus Mastitis Vaccine and Challenged with S. aureus Mastitis Infection.

10.21203/rs.2.20378/v1 ◽

2020 ◽

Author(s):

Idris Umar Hambali ◽

Faez Firdaus Jesse Bin Abdallah ◽

Khaleequl rahaman Bhuttu ◽

Azmi M Lila ◽

zunita Zakaria ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Serum Amyloid A ◽

Acute Phase Proteins ◽

Serum Amyloid ◽

Bacterial Challenge ◽

Amyloid A ◽

Significant Difference ◽

Group B ◽

Pro Inflammatory Cytokines ◽

Friesian Cows

Abstract Background The economic downturn experienced by farmers and the fear of milk borne infection are of a greater public health concern. Haptoglobin, Serum Amyloid A, IL-12 and IL-10 in lactating Friesian cows vaccinated with prototype killed S. aureus mastitis vaccine and challenged with S. aureus were evaluated. Bacterin concentration at 10 8 cfu /ml of the local isolate of S. aureus was adjuvanted with KAl(SO₄)₂. Six lactating Friesian cows were grouped into A= Negative control, B = Positive control and C = vaccine group. Group C was vaccinated intramuscularly with 2ml of the monovalent vaccine, groups A and B with physiologic normal saline. Groups B and C were later challenged with the live bacterium via intramammary route . Result There was a significant increase in IL-10 concentration in vaccinated group post primary vaccination (PPV), booster phase (PB) and during the bacterial challenge phase. There was also a significantly increased IL-12 concentration in the vaccinated group at 24 hours, weeks 1 and 2 PPV. Haptoglobin at 12 and 24 hours PPV had a significant difference in group C. During the PB at 8 and 12 hours there was a significant difference in group C. During the bacterial challenged phase at 0, 3, 24 hours and day 7 PC there was a significant difference in group B. At 8 hours PC there was a significant difference in group C. For Serum Amyloid A, during PPV at 0, 3, 8, 12, 24 hours and weeks 1 and 2, the concentrations was significantly different in groups C. During PB at 0, 3, 8 and 12 hours PB there was a significant difference in groups C. During the bacterial challenge phase at 3, 8, 12, 24 hours, days 7 and 14 PC there was a significant difference in group B. At 0 hour PC there was a significant increase observed in group C. Conclusion The developed prototype killed S. aureus mastitis vaccine using local isolates was able to stimulate acute phase proteins and pro-inflammatory cytokines. The pattern of responses PC indicated protection, thereby suggesting that vaccination can protect against mastitis infection in dairy cows.

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The acute phase response and C-reactive protein

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0239 ◽

2020 ◽

pp. 2199-2207

Author(s):

Mark B. Pepys

Keyword(s):

Acute Phase ◽

Acute Phase Response ◽

Serum Amyloid A ◽

Acute Phase Proteins ◽

Phase Response ◽

Serum Amyloid ◽

C Reactive Protein ◽

Reactive Protein ◽

Amyloid A ◽

Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

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Phosphorylation of human serum amyloid A protein by protein kinase C

Biochemical Journal ◽

10.1042/bj2550029 ◽

1988 ◽

Vol 255 (1) ◽

pp. 29-34 ◽

Cited By ~ 14

Author(s):

A E Nel ◽

M C De Beer ◽

E G Shephard ◽

A F Strachan ◽

M L Vandenplas ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Acute Phase ◽

Serum Amyloid A ◽

Density Lipoprotein ◽

Acute Phase Reactant ◽

Serum Amyloid ◽

Amyloid A ◽

Kinase C ◽

Serum Amyloid A Protein

Monokine-induced hepatic secretion of serum amyloid A protein (apo-SAA), an acute-phase reactant, is followed by rapid association with high-density lipoprotein (HDL) in plasma. Plasma clearance of apo-SAA is more rapid than any of the other HDL apolipoproteins. It has been shown that, of the acute-phase HDL3 apolipoproteins, apo-SAA preferentially associates with neutrophil membranes. HDL apolipoproteins have been shown to activate protein kinase C in endothelial cells. We therefore investigated potential phosphorylation of HDL3 apolipoproteins by protein kinase C. Apo-SAA was the only apolipoprotein phosphorylated (Km = 12 mM). Phosphorylation of the apo-SAA-containing HDL3 particle was selective for the more basic isoforms of apo-SAA (pI 7.0, 7.4, 7.5 and 8.0), with more acidic isoforms being phosphorylated when delipidated acute-phase apolipoproteins were used as substrate. However, phosphorylation was not in itself responsible for the establishment of the apo-SAA isoforms.

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Properties of four acute phase proteins: C-reactive protein, serum amyloid a protein, α1-acid glycoprotein, and fibrinogen

Seminars in Arthritis and Rheumatism ◽

10.1016/0049-0172(90)90055-k ◽

1990 ◽

Vol 20 (3) ◽

pp. 129-147 ◽

Cited By ~ 171

Author(s):

Duane R. Schultz ◽

Patricia I. Arnold

Keyword(s):

Acute Phase ◽

Serum Amyloid A ◽

Acute Phase Proteins ◽

Serum Amyloid ◽

C Reactive Protein ◽

Acid Glycoprotein ◽

Reactive Protein ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Protein Serum

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Evaluation of the systemic acute phase response and endometrial gene expression of serum amyloid A and pro- and anti-inflammatory cytokines in mares with experimentally induced endometritis

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2010.07.011 ◽

2010 ◽

Vol 138 (1-2) ◽

pp. 95-105 ◽

Cited By ~ 43

Author(s):

Christoffersen Mette ◽

Baagoe Camilla Dooleweerdt ◽

Jacobsen Stine ◽

Bojesen Anders Miki ◽

Petersen Morten Roenn ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Cytokines ◽

Acute Phase ◽

Acute Phase Response ◽

Serum Amyloid A ◽

Phase Response ◽

Serum Amyloid ◽

Amyloid A ◽

Anti Inflammatory ◽

Experimentally Induced

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Clinical Relevance of Serum Amyloid a Protein Monitoring in Urinary Tract Infections

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329303000308 ◽

1993 ◽

Vol 30 (3) ◽

pp. 272-277 ◽

Cited By ~ 10

Author(s):

Martin-Tino Časl ◽

Mirjana Sabljar-Matovinović ◽

Sandra Kovačević ◽

Darko Počanić ◽

Vladimira Preden-Kereković ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Acute Phase ◽

Clinical Relevance ◽

Serum Amyloid A ◽

Therapy Monitoring ◽

Serum Amyloid ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Tract Infections

We have evaluated the clinical relevance of monitoring acute phase proteins in severe urinary tract infection. Body temperature, white blood cell count, erythrocyte sedimentation rate, serum amyloid A protein (SAA), C-reactive protein (CRP), α-1-antichymotrypsin (ACT) and α-1-acid glycoprotein (AGP) were determined daily in sera from 18 treated patients. Two patterns of response could be identified: responders and non-responders whose therapy had to be changed. Mean values for each acute phase protein were calculated daily in both responders and non-responders. Statistical evaluation of the significance between the means for each protein was also performed on a daily basis and showed P < 0·01 for SAA and CRP on day 3, for ACT on day 5, and for AGP on day 6. SAA and CRP appear to be the most reliable markers for antimicrobial therapy monitoring in patients with urinary tract infections.

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