PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 7583160

The acute-phase response.

B H Pannen·J L Robotham
View original source ↗Export metadata ↓

Abstract

Inflammation and tissue injury elicit profound changes in the concentrations of several plasma proteins. These proteins are predominantly synthesized in the liver and named acute-phase proteins. The regulatory mechanisms that control this response are highly complex and include the release of various mediators affecting specific subsets of acute-phase genes. Individual mediators can either synergistically enhance or inhibit the effects of other mediators. Binding of mediators to their respective receptors on hepatocytes and transduction of this signal induce changes in acute-phase protein gene expression that are primarily regulated on a transcriptional level. However, under certain conditions post-transcriptional mechanisms may also be involved in this process. Although some acute-phase proteins have been shown to minimize tissue damage, as well as to participate in hemostasis, tissue repair, and regeneration in response to injury, the actual in vivo functions of several acute-phase reactants remain speculative. Measurements of acute-phase protein plasma concentrations can be of diagnostic or prognostic value under certain clinical conditions. Further characterization of the regulatory mechanisms that govern the acute-phase response in vivo could lead to the development of new therapeutic strategies aimed at improving the organism's integrated response to injury.

Explore related subjects

Acute-Phase ProteinsAcute-Phase ReactionAnimalsCytokinesGene ExpressionHumansSignal TransductionJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

B H Pannen, J L Robotham. 1995. The acute-phase response.. https://pubmed.ncbi.nlm.nih.gov/7583160/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1998

The induction of acute phase proteins by lipopolysaccharide uses a novel pathway that is CD14-independent.

LPS (endotoxin) and proinflammatory cytokines (IL-6, IL-1, and TNF-alpha) are potent inducers of acute phase proteins (APP). Since LPS induces high levels of these cytokines after its interaction with CD14, a protein expressed on the surface of monocytes and neutrophils, it has been assumed that CD14 mediates the LPS induction of APP expression. To test this hypothesis, CD14-deficient and control mice were injected with low doses of LPS, and the expression of several APP that are normally up-regulated by LPS was measured. CD14-deficient mice showed no alteration in the induction of APP, including serum amyloid A, LPS-binding protein, fibrinogen, or ceruloplasmin; in contrast, C3H/HeJ mice, which carry a mutation in the Lps gene, do not up-regulate the expression of these proteins. These studies show that the up-regulation of APP by LPS utilizes a non-CD14 receptor and requires a functional Lps gene.

Acute-Phase Proteins↗
PubMed1998

Increased pentosidine, an advanced glycation end product, in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with inflammatory markers.

Pentosidine is an advanced glycation end product (AGE) formed by combined processes of glycation and oxidation (glycoxidation) between carbohydrate-derived carbonyl group and protein amino group. Recent studies demonstrated the increased pentosidine levels not only in diabetic patients with hyperglycemia but also in normoglycemic uremic patients due to increased oxidative stress. Rheumatoid arthritis (RA) is a state of increased oxidative stress associated with chronic inflammation. This suggested an enhanced glycoxidation reaction and increased AGE levels in RA patients. In the present study, we therefore determined, by high performance liquid chromatographic (HPLC) assay, the concentrations of pentosidine in plasma and synovial fluid from 22 patients with rheumatoid arthritis (RA) and compared their levels with those in 17 patients with osteoarthritis (OA), 26 diabetic patients, and 25 normal subjects. The levels of inflammatory markers and markers of tissue destruction, metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), were also measured in the same samples. Pentosidine levels in plasma and synovial fluid from RA patients were significantly higher than those in OA patients, diabetic patients, and normal subjects. There was a significant correlation between the pentosidine levels in plasma and those in synovial fluid. Among markers of inflammation and matrix destruction, pentosidine levels in plasma from RA patients were correlated with the levels of C-reactive protein (CRP), erythrocyte sedimentation rate, white blood cell count, and platelet count. Multiple stepwise regression analysis reveals an independent influence of CRP on plasma pentosidine levels. In conclusion, pentosidine levels are significantly higher in plasma and synovial fluid from RA patients and may be useful as a biomarker of chronic inflammation in RA patients.

Acute-Phase Proteins↗
PubMed1998

Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate alpha1-antichymotrypsin expression in human cortical astrocytes.

alpha1-Antichymotrypsin (ACT) is an acute phase protein expressed in the brain which specifically colocalizes with amyloid-beta during Alzheimer's disease. We analyzed ACT synthesis in cultured human cortical astrocytes in response to various cytokines and growth factors. Oncostatin M (OSM) and interleukin (IL)-1beta were potent stimulators of ACT mRNA expression, whereas tumor necrosis factor-alpha had modest activity, and IL-6 and leukemia inhibitory factor (LIF) were ineffective. The finding that OSM, but not LIF or IL-6, stimulated ACT expression suggests that human astrocytes express a "specific" OSM receptor, but not IL-6 or LIF receptors. However, cotreatment of human astrocytes with soluble IL-6 receptor (sIL-6R).IL-6 complex did result in potent stimulation of ACT expression. When the human ACT gene was cloned, two elements binding STAT1 and STAT3 (signal transducer and activator of transcription) in response to OSM or IL-6.sIL-6R complexes could be identified and characterized. Taken together, these findings indicate that OSM or IL-6.sIL-6 complexes may regulate ACT expression in human astrocytes and thus directly or indirectly contribute to the pathogenesis of Alzheimer's disease.

Acute-Phase Proteins↗