The acute phase response: General aspects

Kushner, Irving; Rzewnicki, Debra

doi:10.1016/s0950-3579(05)80113-x

Cited by 129 publications

(105 citation statements)

References 75 publications

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“…In the short-term, the acute-phase response has survival value and is designed to restore homeostasis after environmental threats [3]; we hypothesise that long-term activation produces disease instead of repair in subjects who develop Type II diabetes.…”

Section: : 1241±1248]mentioning

confidence: 99%

Is Type II diabetes mellitus a disease of the innate immune system?

1998

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The cause of the common type of Type II (non-insulin-dependent) diabetes mellitus, which affects at least 100 million people throughout the world, is not known. One of the foremost challenges we face is to account mechanistically for not only the defining hyperglycaemia but also for the myriad of other biochemical and physiological abnormalities which are characteristic of this disease. For example, it is now clear that Type II diabetes and lesser degrees of glucose intolerance commonly occur together with a collection of clinical and biochemical features which have been called metabolic syndrome X [1, 2].These features include central obesity, hypertension, accelerated atherosclerosis, hypertriglyceridaemia and low serum concentrations of high-density lipoprotein (HDL) cholesterol. Though insulin resistance seems to be a central abnormality, the origin of the impaired insulin action and how it explains the many other abnormalities of Type II diabetes is not known.In recent years, we have been gathering evidence that in Type II diabetes there is a cytokine-associated acute-phase reaction, part of the innate immune response. As an alternative direction for research into the aetiology of Type II diabetes, we propose that it may be helpful to consider whether the mechanisms involved in the acute-phase response can be major contributors to the pathophysiology of many of the features of Type II diabetes and syndrome X, including glucose intolerance, insulin resistance, impair- Diabetologia (1998) Summary Type II (non-insulin-dependent) diabetes mellitus is associated with increased blood concentrations of markers of the acute-phase response, including sialic acid, a-1 acid glycoprotein, serum amyloid A, C-reactive protein and cortisol, and the main cytokine mediator of the response, interleukin-6. The dyslipidaemia common in Type II diabetes (hypertriglyceridaemia and low serum levels of HDL cholesterol) is also a feature of natural and experimental acutephase reactions. We review evidence that a long-term cytokine-mediated acute-phase reaction occurs in Type II diabetes and is part of a wide-ranging innate immune response. Through the action of cytokines on the brain, liver, endothelium, adipose tissue and elsewhere, this process could be a major contributor to the biochemical and clinical features of metabolic syndrome X (glucose intolerance, dyslipidaemia, insulin resistance, hypertension, central obesity, accelerated atherosclerosis) but also provides a mechanism for many other abnormalities seen in Type II diabetes, including those in blood clotting, the reproductive system, metal ion metabolism, psychological behaviour and capillary permeability. In the short-term, the innate immune system restores homeostasis after environmental threats; we suggest that in Type II diabetes and impaired glucose tolerance long-term lifestyle and environmental stimulants, probably in those with an innately hypersensitive acute-phase response, produce disease instead of repair. [Diabetologia (1998

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Section: : 1241±1248]mentioning

confidence: 99%

Is Type II diabetes mellitus a disease of the innate immune system?

1998

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“…1A). For apoSAA1 this reaction generated an insoluble 16-mer (apoSAA [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] ), and two soluble fragments, a 7-mer (apoSAA1 [17][18][19][20][21][22][23] ) and an 80-mer (apoSAA1 24 -103 ) which constituted about 78% of the native protein. For apoSAA2 a substitution of Ile with Met at residue 76 introduces an additional cleavage site allowing the 80-mer to be cleaved into a 53-mer (apoSAA2 24 -76 ) and a 27-mer (apoSAA2 ) (Fig.…”

Section: Cyanogen Bromide Cleavage Of Rp-hplc-purified Aposaa1mentioning

confidence: 99%

“…B, apoSAA1 and apoSAA2 isoforms eluted at 27.2 and 29 min, respectively. C, the apoSAA1 CNBr peptides, a 7-mer (apoSAA1 [17][18][19][20][21][22][23] ), an 80-mer (apoSAA1 24 -103 ), and a 16-mer (apoSAA1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] ), eluted at 18.3, 25.6, and 29 min, respectively. D, the apoSAA2 CNBr peptides, a 7-mer (apoSAA2 [17][18][19][20][21][22][23] ), a 27-mer (apoSAA2 ), a 53-mer (apoSAA2 24 -76 ), and a 16-mer (apoSAA2 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] M NaCl (RT ϭ 37.9 min) on heparin-Sepharose 4B (Fig.…”

Section: Cyanogen Bromide Cleavage Of Rp-hplc-purified Aposaa1mentioning

confidence: 99%

“…In response to tissue injury or infection, activated macrophages secrete cytokines (interleukin-1 and -6 and tumor necrosis factor) that induce liver synthesis of a number of acutephase (AP) 1 proteins (1,2). The function of most of the AP proteins is unknown, but it is widely accepted that their purpose is to enhance host survival by neutralizing infectious agents, contributing to tissue repair, and restoring homeostasis.…”

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confidence: 99%

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The Heparin/Heparan Sulfate-binding Site on Apo-serum Amyloid A

Ancsin

Kisilevsky

1999

Journal of Biological Chemistry

147

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Serum amyloid A isoforms, apoSAA1 and apoSAA2, are apolipoproteins of unknown function that become major components of high density lipoprotein (HDL) during the acute phase of an inflammatory response. ApoSAA is also the precursor of inflammation-associated amyloid, and there is strong evidence that the formation of inflammation-associated and other types of amyloid is promoted by heparan sulfate (HS). Data presented herein demonstrate that both mouse and human apoSAA contain binding sites that are specific for heparin and HS, with no binding for the other major glycosaminoglycans detected. Cyanogen bromide-generated peptides of mouse apoSAA1 and apoSAA2 were screened for heparin binding activity. Two peptides, an apoSAA1-derived 80-mer (residues 24 -103) and a smaller carboxyl-terminal 27-mer peptide of apoSAA2 (residues 77-103), were retained by a heparin column. A synthetic peptide corresponding to the CNBr-generated 27-mer also bound heparin, and by substituting or deleting one or more of its six basic residues (

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“…Despite the numerous association studies with these single-nucleotide polymorphisms (SNPs), and studies on in vivo circulating IL-6 levels, in vitro gene expression and luciferase reporter assays (reviewed in Smith and Humphries 3 ), there is no conclusive evidence of IL6-SNP functionality. Indeed, among genome-wide association studies (GWAS) for C-reactive protein (CRP) level, which is strongly determined by IL-6 level, 8 no studies have found any association of the IL6 locus with Caucasian individuals, although associations have been seen for variants at IL6R and CRP. 9,10 A recent GWAS for CRP levels did identify a distal IL6 promoter SNP, rs2097677 (430 kb upstream to the IL6 transcription start site), within a large Japanese cohort, 11 although this has not been replicated in other populations.…”

Section: Introductionmentioning

confidence: 99%

Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus

et al. 2012

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The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the three putative functional IL6 promoter variants, À 174G4C, À 572G4C and À 6331T4C, two complementary techniques, allele-specific chromatin immunoprecipitation and allele-specific formaldehydeassisted isolation of regulatory elements, were carried out using unrelated lymphoblast cell lines of known genotype. There were no allele-specific effects for all three single-nucleotide polymorphisms (SNPs) under basal conditions. Upon IL-1b stimulation, however, allele-specific effects were seen for the À 6331 allele, which showed both increased RNA polymerase II loading (56%, P ¼ 0.001) and increased open chromatin (59%, P ¼ 0.004) for the T allele, which is in line with previous reports of this SNP and the effects from acute inflammation. These studies highlight the importance of examining chromatin under different environmental conditions when studying the functionality of regulatory polymorphisms.

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The acute phase response: General aspects

Cited by 129 publications

References 75 publications

Is Type II diabetes mellitus a disease of the innate immune system?

Is Type II diabetes mellitus a disease of the innate immune system?

The Heparin/Heparan Sulfate-binding Site on Apo-serum Amyloid A

Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus

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