Serum amyloid A induces IL-8 secretion through a G protein–coupled receptor, FPRL1/LXA4R

Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1572-1581 ◽  
Author(s):  
Rong He ◽  
Hairong Sang ◽  
Richard D. Ye

Host response to injury and infection is accompanied by a rapid rise in the blood of acute-phase proteins such as serum amyloid A (SAA). Although SAA has been used as a marker for inflammatory diseases, its role in the modulation of inflammation and immunity has not been defined. Human neutrophils respond to SAA with secretion of the proinflammatory cytokines interleukin 8 (IL-8) and, to a lesser extent, tumor necrosis factor α (TNF-α). The induction of IL-8 secretion by SAA involves both transcription and translation and correlates with activation of nuclear factor κB (NF-κB). The proximal signaling events induced by SAA include mobilization of intracellular Ca2+ and activation of the mitogen-activated protein kinases ERK1/2 and p38, both required for the induced IL-8 secretion. Pertussis toxin effectively blocks SAA-induced IL-8 secretion indicating involvement of a Gi-coupled receptor. Overexpression of FPRL1/LXA4R in HeLa cells results in a significant increase of the expression of NF-κB and IL-8 luciferase reporters by SAA, and an antibody against the N-terminal domain of FPRL1/LXA4R inhibits IL-8 secretion. Lipoxin A4, which binds to FPRL1/LXA4R specifically, decreases SAA-induced IL-8 secretion significantly. Collectively, these results indicate that the cytokine-like property of SAA is manifested through activation of the Gi-coupled FPRL1/LXA4R, which has been known to mediate the anti-inflammatory effects of lipoxin A4. The ability of FPRL1/LXA4R to mediate 2 drastically different and opposite functions suggests that it plays a role in the modulation of inflammatory and immune responses.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3855-3855
Author(s):  
Rong He ◽  
Jian Zhou ◽  
Richard D. Ye

Abstract Host response to injury and infection is accompanied by a rapid rise of acute-phase proteins in the blood. Serum amyloid A (SAA) is a major acute-phase protein, and has been used as a marker for inflammatory diseases. However, its precise role in inflammation has not been defined. In our previous study, we found that SAA can induce IL-8 and TNF-alpha secretion from peripheral blood neutrophils, which indicates that SAA has cytokine-like functions. We have also identified SAA as an endogenous ligand that induces the expression of interleukin-23 (IL-23), a hetero-dimeric cytokine that promotes autoimmune inflammation. In this study, we reported that SAA stimulates monocytes to secret granulocyte colony-stimulated factor (G-CSF), a cytokine and a major hematopoietic growth factor. Injection of SAA into mouse peritoneum significantly increases the number of neutrophils in both peritoneal cavity and blood circulation. These results suggest that SAA can induce granulocytosis during infection and inflammation. We hypothesize that during the inflammation, locally or systematically produced SAA can increase the number of neutrophils in blood circulation and recruits them to injured or infected sites through induction of G-CSF.


2019 ◽  
Vol 36 (3) ◽  
pp. 198-201
Author(s):  
Sheri S. W. Birmingham ◽  
Rocky M. Mason

Serum amyloid A (SAA) is one of the major acute phase proteins in horses. It serves as a marker for systemic inflammation and infection, as the concentration can increase 100- to even 1000-fold during systemic disease processes. The objective of this study was to evaluate the effect of sedation, oral examination, and odontoplasty on systemic inflammation as measured by SAA in the adult performance horse. This study included 32 clinically healthy adult performance horses. Blood samples were collected immediately prior to sedation, oral examination, and odontoplasty and 48 and 72 hours afterward. Serum amyloid A levels were measured directly after venipuncture using a commercially available stall-side lateral flow immunoassay test developed and validated for equine SAA levels. Serum amyloid A values were within normal limits for each of the time periods and there were no significant differences in SAA values between the time periods. The results of this study suggest that sedation, oral examination, and odontoplasty have no systemic inflammatory effects as measured by SAA.


Author(s):  
Syed Wali Peeran ◽  
Ahmed Elhassan ◽  
Mohammed Zameer ◽  
Syed Nahid Basheer ◽  
Mohammed Mustafa ◽  
...  

Serum Amyloid A (SAA) is an Acute-Phase Protein (APP) produced as an innate nonspecific response to any tissue damage. Hence, it plays a significant role in chronic inflammatory diseases. In particular, SAA levels increase dramatically in chronic periodontitis and chronic apical periodontitis. Recent studies suggest this role of SAA in the pathogenesis of various diseases, including chronic periodontitis and chronic apical periodontitis. Thus, the focus of this review is to sum up the current understanding of the role of SAA in health and disease and to elaborate on possible mechanisms by which SAA could play a role in the pathogenesis of chronic periodontitis and chronic apical periodontitis.


2020 ◽  
Author(s):  
Idris Umar Hambali ◽  
Faez Firdaus Jesse Bin Abdallah ◽  
Khaleequl rahaman Bhuttu ◽  
Azmi M Lila ◽  
zunita Zakaria ◽  
...  

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.


2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys

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.


Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1756
Author(s):  
Katie L. Edwards ◽  
Michele A. Miller ◽  
Jessica Siegal-Willott ◽  
Janine L. Brown

Serum biomarkers indicative of inflammation and disease can provide useful information regarding host immune processes, responses to treatment and prognosis. The aims of this study were to assess the use of commercially available anti-equine reagents for the quantification of cytokines (tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL) 2, 6, and 10) in African (Loxodonta africana, n = 125) and Asian (Elephas maximus, n = 104) elephants, and alongside previously validated anti-human reagents for acute-phase proteins (serum amyloid A and haptoglobin), calculate species-specific biomarker value ranges. In addition, we used opportunistically collected samples to investigate the concentrations of each biomarker during identified clinical cases of illness or injury, as a first step to understanding what biomarkers may be useful to managing elephant health. Immune biomarkers were each elevated above the calculated species-specific value ranges in at least one clinical case, but due to variability in both clinical and non-clinical samples, only serum amyloid A was significantly higher in clinical compared to non-clinical paired samples, with tendencies for higher TNF-α and IL-10. We also detected increased secretion of serum amyloid A and all five cytokines following routine vaccination of a single Asian elephant, indicating that these biomarkers can be beneficial for studying normal immune processes as well as pathology. This study indicates that assays developed with commercial reagents can be used to quantify health biomarkers in wildlife species and identifies several that warrant further investigation to elucidate immune responses to various pathologies.


2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Birsen Ucar ◽  
Bilal Yildiz ◽  
M. Arif Aksit ◽  
Coskun Yarar ◽  
Omer Colak ◽  
...  

Background. Sepsis is an important cause of mortality in newborns. However, a single reliable marker is not available for the diagnosis of neonatal late-onset sepsis (NLS). The aim of this study is to evaluate the value of serum amyloid A (SAA) and procalcitonin (PCT) in the diagnosis and follow-up of NLS.Methods. 36 septic and healthy newborns were included in the study. However, SAA, PCT, TNF-α, IL-1β, and CRP were serially measured on days 0, 4, and 8 in the patients and once in the controls. Töllner's sepsis score (TSS) was calculated for each patient.Results. CRP, PCT, and TNF-αlevels in septic neonates at each study day were significantly higher than in the controls (P=.001). SAA and IL-1βlevels did not differ from healthy neonates. The sensitivity and specificity were 86.8% and 97.2% for PCT, 83.3% and 80.6% for TNF-α, 75% and 44.4% for SAA on day 0.Conclusion. Present study suggests that CRP seems to be the most helpful indicator and PCT and TNF-αmay be useful markers for the early diagnosis of NLS. However, SAA, IL-1β, and TSS are not reliable markers for the diagnosis and follow-up of NLS.


2013 ◽  
Vol 44 (1) ◽  
pp. 103 ◽  
Author(s):  
Beth Wells ◽  
Giles T Innocent ◽  
Peter D Eckersall ◽  
Eilidh McCulloch ◽  
Alasdair J Nisbet ◽  
...  

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