Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine serum amyloid A1 (SAA1) and serum amyloid A2 (SAA2) are circulating, acute phase, high density apolipoproteins of unknown function. To pursue issues relating to their possible function their uptake and formation were studied. Kinetics of SAA protein distribution and gene expression after acute phase stimulation by casein or lipopolysaccharide were examined using immunocytochemistry for protein and RNA blot and in situ hybridization with probes for SAA1 and SAA2 mRNA. After casein injection, interstitial cells of testes, cells of adrenal cortex, kidney proximal convoluted tubule epithelia, and some parafollicular cells of spleen took up SAA in a time pattern related to plasma SAA levels. Extrahepatic SAA1 and SAA2 mRNA were induced by lipopolysaccharide in kidney proximal and distal convoluted tubule epithelia, and SAA1 mRNA was induced in epithelial lining the mucosa of the ileum and large intestine, indicating that there may be more than one function for the apoSAA gene family related to site of and stimulus for expression.
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PMID:Serum amyloid A in the mouse. Sites of uptake and mRNA expression. 278 80

We examined the effect of endotoxemia in mice on protein and mRNA levels for the acute phase proteins complement C3 and serum amyloid A (SAA) in jejunal mucosa. Endotoxemia was induced in mice by the subcutaneous injection of 250 microg lipopolysaccharide per mouse. Control mice were injected with saline. C3 and SAA were measured by ELISA. Messenger RNA levels were determined by Northern blot analysis or competitive PCR. Immunohistochemistry was performed to determine in which cell type(s) C3 and SAA were present. Mucosal C3 and SAA protein and mRNA levels were increased in endotoxemic mice. Immunohistochemistry showed that C3 was present in both enterocytes and cells of the lamina propria, whereas SAA was seen mainly in lamina propria cells. Results suggest that endotoxemia stimulates production of C3 and SAA in small intestinal mucosa. The response may be regulated at the transcriptional level and probably reflects increased synthesis of the acute phase proteins in both enterocytes and cells of the lamina propria.
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PMID:Endotoxemia in mice stimulates production of complement C3 and serum amyloid A in mucosa of small intestine. 979 Oct 77

Serum amyloid A (SAA) proteins are acute-phase apolipoproteins that are associated with high-density lipoprotein (HDL) particles: SAA proteins are precursors to secondary amyloid fibril proteins and under certain conditions of chronic or recurrent inflammation these proteins are deposited as amyloid fibrils. Of two isotypes found in mouse, SAA1.1 and SAA2.1, only SAA1.1 is deposited into amyloid. The CE/J mouse is unique, in that the only isoform identified is a hybrid between SAA1.1 and SAA2.1 and the mouse does not show amyloid deposition. In the rat, a deletion in the SAA1/SAA2 gene is associated with the absence of protein in the plasma and subsequently no amyloid deposition is detected. We have generated adenoviral vectors to study the expression of SAA proteins on HDL metabolism and amyloid formation. Injection of SAA viruses into rats resulted in expression of the mouse SAA proteins in the plasma with specific association of the SAA with HDL particles. The induction of SAA proteins was comparable to that seen in mice presented with the inflammatory agent, bacterial lipopolysaccharide (LPS). Adenoviral induced SAA levels were maintained for up to several weeks without a significant decrease in SAA expression. Injection of rats with the mouse SAA1.1 adenoviral vector, followed by amyloid enhancing factor (AEF) and silver nitrate resulted in the deposition of amyloid fibrils in the spleen. After 2 weeks, amyloid could be detected in other tissues, including the heart, liver, kidneys and lungs. When animals were injected with null or the SAA2.2 virus no amyloid was detected. These studies demonstrate that the inability of the rat to develop AA amyloid is due to the lack of synthesizing an amyloidogenic SAA protein. Furthermore, the expression of the adenoviral SAA protein from the liver and incorporation onto HDL particles further supports the hypothesis that AA amyloid is derived from circulating SAA protein. The ease of use of the adenoviral vectors and the rat provide an excellent model to study the function of SAA proteins.
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PMID:Amyloid formation in the rat: adenoviral expression of mouse serum amyloid A proteins. 1084 3

Acute phase proteins such as serum amyloid A proteins (SAAs) and serum amyloid P component (SAP) are induced in the liver after various insults (e.g., infection, injury). The cellular and molecular mechanisms controlling the expression of these acute phase proteins may be specifically designed for different insults. The roles of two central molecules of the lipopolysaccharide (LPS)-mediated inflammation pathway (CD14 and toll-like receptor 4 [Tlr4]) were investigated for the regulation of SAAs and SAP in the liver of mice after an 18% total body surface area burn injury. RT-PCR analysis revealed a subtype- and time-dependent induction of SAA mRNAs between 3 h and 3 days, while there was a peak induction of SAP mRNA at day 1. Marked elevations of SAA and SAP protein levels at day 1 supported the mRNA data. Furthermore, a differential regulation of SAAs and SAP mRNAs was noted between CD14 knockout (KO) and their control mice after injury. SAA protein was induced to a lesser degree after injury in C3H/HeJ (Tlr4-defective) mice than in their control mice. In addition, in both CD14 KO and C3H/HeJ mice, the induction of SAP protein was significantly reduced compared with respective controls. These data provide evidence that CD14 and Tlr4 participate, at least in part, in a cascade of signaling events that control the immediate-early and differential induction of SAAs and SAP in the liver after injury. They also suggest that LPS may be one of the initial inducing agents associated with these acute phase responses in the liver after injury.
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PMID:Involvement of CD14 and toll-like receptor 4 in the acute phase response of serum amyloid A proteins and serum amyloid P component in the liver after burn injury. 1475 88

Serum amyloid A (SAA) is synthesized by the liver during the acute phase. Local expression of SAA mRNA has been reported also in non-liver cells, a potential local source of SAA protein not related to the systemic acute phase response. SAA function has not been established yet. In the present study, we identified SAA as a protein expressed by chondrocytes and myoblasts in response to inflammatory stimula. In both cell systems, SAA mRNA and protein expression is strongly stimulated by bacterial lipopolysaccharide treatment. SAA mRNA expression is also enhanced during terminal differentiation of cells of the chondrogenic and myogenic lineage; mRNA is barely detectable in prechondrogenic cells and is highly expressed in differentiated hyperthrophic chondrocytes. An increased level of SAA mRNA was also observed in vivo when we compared mRNA extracted from tibiae of 10 day embryos, still fully cartilaginous, with tibiae from 18 day embryos, a stage when the endochondral ossification process has already started. p38 activation, a well-known event of the chondrogenesis signaling cascade, controls expression of SAA in cartilage following inflammatory stimuli. SAA secreted by stimulated chondrocytes is associated with cholesterol. Cholesterol is synthesized by the same chondrocytes and is also increased in inflammatory conditions. A role of SAA in cholesterol homeostasis in chondrocytes is proposed.
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PMID:Expression of serum amyloid A in chondrocytes and myoblasts differentiation and inflammation: possible role in cholesterol homeostasis. 1517 36

In brown chicken with chronic inflammatory processes of the joints amyloid arthropathy easily develops. The amyloid has been shown to be of the AA type which is derived from serum amyloid A (SAA). The aim of the present study was to investigate whether fibroblast-like synoviocytes (FLS) originating from brown chicken and other chicken breeds express SAA mRNA and produce SAA protein. FLS were isolated from the knee joint synovium of healthy brown chickens, white chickens, and broilers. The absence of macrophages in FLS cultures was confirmed by assessment of the phagocytic capability and by immunohistochemistry. Additionally, cultured cells were identified by electron microscopy and immunohistochemical staining. Expression of SAA mRNA in normal and lipopolysaccharide (LPS)-stimulated cells was assessed by in situ hybridization, Northern blot analysis, reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis and real-time quantitative PCR. SAA protein production was analyzed by Western blotting and ELISA. SAA mRNA was detected in unstimulated FLS isolated from the three different chicken breeds and more abundantly in those stimulated with LPS. However, SAA protein production was only detected in culture medium and cell lysate of LPS-stimulated FLS. Furthermore, FLS produced SAA in a concentration-dependent manner after stimulation with different amounts of LPS. The data suggest that during infection and inflammation chicken FLS may act as a source of articular SAA. This process may enhance development of amyloid from SAA in the joint.
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PMID:Serum amyloid A production by chicken fibroblast-like synoviocytes. 1591 Sep 91

Serum amyloid A (SAA) is one of the major acute phase proteins in cats and humans. SAA concentrations increase in response to the inflammatory status and secondary amyloid A amyloidosis has been documented in cats. In order to control the SAA concentration, it is important to clarify how the SAA protein is metabolized. Although the details of SAA metabolism in the body remain unknown, human and murine research indicates that macrophages play a key role in SAA uptake. The objectives of this study were to demonstrate SAA uptake by feline macrophages and to evaluate the effects of lipopolysaccharide (LPS) and dexamethasone (Dex) on SAA uptake. The concentration of recombinant feline SAA added to a feline macrophage culture was decreased in a time-dependent manner and was significantly reduced after a 24-h incubation, as demonstrated by enzyme linked immunosorbent assay (ELISA). SAA uptake into feline peripheral macrophages was demonstrated by immunofluorescence microscopy. Pretreatment to macrophages with LPS did not affect this decrease in the SAA concentration, but this was significantly blocked by Dex pretreatment. In conclusion, SAA was incorporated by feline macrophages and pretreatment with Dex inhibited SAA uptake by macrophages in this study. Further investigation is needed to determine the molecules that influence SAA uptake by macrophages and the effect of clinical glucocorticoid usage on the SAA concentration in cats.
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PMID:Serum amyloid A uptake by feline peripheral macrophages. 2294 61

Vaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positive Streptococcus pneumoniae serotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.
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PMID:Immunization with pneumococcal polysaccharide serotype 3 and lipopolysaccharide modulates lung and liver inflammation during a virulent Streptococcus pneumoniae infection in mice. 2338 32