Role of Serum Amyloid A as an Intermediate in the IL-1 and PMA-Stimulated Signaling Pathways Regulating Expression of Rabbit Fibroblast Collagenase

Strissel, Katherine J.; Girard, M T; West‐Mays, Judith A.; Rinehart, William B.; Cook, Jacob; Brinckerhoff, Constance E.; Fini, M. Elizabeth

doi:10.1006/excr.1997.3783

Cited by 39 publications

(23 citation statements)

References 40 publications

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“…The list of cardiac fibroblast specific transcripts contains many extracellular 5 matrix proteins, e.g., collagens and other regulatory extracellular proteins such as annexin 1, metalloproteinase-3 and the inhibitor of metalloproteinase-3. Our data also agree with reports of the presence of amyloid A3 and prion protein in fibroblasts [21,22]. However, unlike previous data, SAGE gives quantitative information about the expression level of these different gene products.…”

Section: Comparison Of Cardiac Fibroblast and Total Heart Gene Expressupporting

confidence: 92%

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

et al. 2004

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SummaryCardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signalling pathways. The NO/cGMP signalling pathway was represented by the mRNAs for α 1 and β 1 subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I) and interestingly the G-kinase anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western Blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP-analog inhibited the proliferation of serum-stimulated cardiac fibroblasts which express cGK I, but not higher passage fibroblasts which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth.Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.

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Section: Comparison Of Cardiac Fibroblast and Total Heart Gene Expressupporting

confidence: 92%

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

et al. 2004

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“…In vitro studies have suggested a number of pathways for the involvement of SAA in host defense mechanisms and inflammation. For example, in vitro experiments and studies in experimental animals indicate that apolipoprotein SAA can induce the expression of proteinases thought to degrade extracellular matrix (87,88), which might be important during tissue injury. Moreover, it can act as a chemoattractant for inflammatory cells such as monocytes, polymorphonuclear leukocytes, and T-lymphocytes (89,90), all of which are involved in host defense mechanisms.…”

Section: Saamentioning

confidence: 99%

Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?

Chait

Oram

Heinecke

2005

Journal of Lipid Research

209

159

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In humans, a chronically increased circulating level of C-reactive protein (CRP), a positive acute-phase reactant, is an independent risk factor for cardiovascular disease. This observation has led to considerable interest in the role of inflammatory proteins in atherosclerosis. In this review, after discussing CRP, we focus on the potential role in the pathogenesis of human vascular disease of inflammation-induced proteins that are carried by lipoproteins. Serum amyloid A (SAA) is transported predominantly on HDL, and levels of this protein increase markedly during acute and chronic inflammation in both animals and humans. Increased SAA levels predict the risk of cardiovascular disease in humans. Recent animal studies support the proposal that SAA plays a role in atherogenesis. Evidence is accruing that secretory phospholipase A 2 , an HDL-associated protein, and platelet-activating factor acetylhydrolase, a protein associated predominantly with LDL in humans and HDL in mice, might also play roles both as markers and mediators of human atherosclerosis. In contrast to positive acute-phase proteins, which increase in abundance during inflammation, negative acutephase proteins have received less attention. Apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, decreases during inflammation. Recent studies also indicate that HDL is oxidized by myeloperoxidase in patients with established atherosclerosis. These alterations may limit the ability of apoA-I to participate in reverse cholesterol transport. Paraoxonase-1 (PON1), another HDL-associated protein, also decreases during inflammation. PON1 is atheroprotective in animal models of hypercholesterolemia. Controversy over its utility as a marker of human atherosclerosis may reflect the fact that enzyme activity rather than blood level (or genotype) is the major determinant of cardiovascular risk. Thus, multiple lipoprotein-associated proteins that change in concentration during acute and chronic inflammation may serve as markers of cardiovascular disease. In future studies, it will be important to determine whether these proteins play a causal role in atherogenesis.

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“…5). It is believed that locally synthesized SAA by synovial cells in the inflamed joints plays a key role in the pathogenesis of rheumatoid arthritis (17,18,20). SAA can be used as a marker for evaluating the efficacy of therapeutics for rheumatoid arthritis.…”

Section: Figurementioning

confidence: 99%

“…A-SAAs have been found in the synovial fluid recovered from inflamed joints of rheumatoid arthritis patients (15), and it is synthesized locally in the synovial membrane (16) by fibroblasts (17) and chondrocytes (18) as a result of the presence of high levels of proinflammatory cytokines, such as IL-1 and IL-6 in the synovial fluid of these patients (19). It is believed that locally synthesized SAA by synovial cells in the inflamed joints acts as an autocrine inducer of matrix metalloproteinase-1 (collagenase), the only enzyme that degrades interstitial collagens I, II, and III and causes extensive joint erosion (17,18,20). In addition, induction of SAA by proinflammatory cytokines has been reported in many other cell types, including macrophages, endothelial cells, smooth muscle cells, and adipocytes of coronary and carotid arteries in human atherosclerotic lesions (21); intestinal epithelial cells (22); and the brain of patients with Alzheimer's disease (23).…”

mentioning

confidence: 99%

Serum Amyloid A-Luciferase Transgenic Mice: Response to Sepsis, Acute Arthritis, and Contact Hypersensitivity and the Effects of Proteasome Inhibition

Zhang¹,

Ahsan²,

Purchio³

et al. 2005

The Journal of Immunology

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Acute phase serum amyloid A proteins (A-SAAs) are multifunctional apolipoproteins produced in large amounts during the acute phase of an inflammation and also during the development of chronic inflammatory diseases. In this study we present a Saa1-luc transgenic mouse model in which SAA1 gene expression can be monitored by measuring luciferase activity using a noninvasive imaging system. When challenged with LPS, TNF-α, or IL-1β, in vivo imaging of Saa1-luc mice showed a 1000- to 3000-fold induction of luciferase activity in the hepatic region that peaked 4–7 h after treatment. The induction of liver luciferase expression was consistent with an increase in SAA1 mRNA in the liver and a dramatic elevation of the serum SAA1 concentration. Ex vivo analyses revealed luciferase induction in many tissues, ranging from several-fold (brain) to >5000-fold (liver) after LPS or TNF-α treatment. Pretreatment of mice with the proteasome inhibitor bortezomib significantly suppressed LPS-induced SAA1 expression. These results suggested that proteasome inhibition, perhaps through the NF-κB signaling pathway, may regulate SAA1 expression. During the development of acute arthritis triggered by intra-articular administration of zymosan, SAA1 expression was induced both locally at the knee joint and systemically in the liver, and the induction was significantly suppressed by bortezomib. Induction of SAA1 expression was also demonstrated during contact hypersensitivity induced by topical application of oxazolone. These results suggest that both local and systemic induction of A-SAA occur during inflammation and may contribute to the pathogenesis of chronic inflammatory diseases associated with amyloid deposition.

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Role of Serum Amyloid A as an Intermediate in the IL-1 and PMA-Stimulated Signaling Pathways Regulating Expression of Rabbit Fibroblast Collagenase

Cited by 39 publications

References 40 publications

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?

Serum Amyloid A-Luciferase Transgenic Mice: Response to Sepsis, Acute Arthritis, and Contact Hypersensitivity and the Effects of Proteasome Inhibition

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