Amyloid A gene family expression in different mouse tissues.

Abstract

Serum amyloid A (SAA) is a major acute-phase reactant and apoprotein of high density lipoprotein (HDL). SAA is encoded by a family of three active genes. We examined hepatic expression and searched for extrahepatic expression of the three SAA mRNAs after injection with casein or LPS. Studies using an SAA cDNA, which detects all three SAA mRNAs, revealed that after casein injection liver SAA mRNA was elevated approximately 1,000-fold. Adrenal gland expressed SAA mRNA at a low level (0.5% of hepatic level), and was the only extrahepatic tissue with elevated SAA mRNA after casein injection. The small intestine, primarily the ileum, and the large intestine of unstimulated control animals contained 5- and 15-fold higher SAA mRNA levels than control liver. LPS also elevated liver SAA mRNA approximately 1,000-fold. However, in contrast to casein injection, every extrahepatic tissue examined expressed SAA mRNA. Lung and kidney contained 2-5% and large intestine contained nearly 10% of SAA mRNA levels found in liver RNA. SAA mRNA levels were lower in the remaining tissues and ranged from 0.1% in the brain and pancreas to 1.0% in the small intestine, with the ileum containing 50-fold more than the duodenum. Analysis of liver with SAA1, SAA2, and SAA3 mRNA-specific oligonucleotide probes revealed that SAA1 and SAA2 mRNA were elevated approximately 50-fold higher than SAA3 mRNA after casein administration. LPS, however, induced all three SAA mRNAs equally. In extrahepatic tissues, SAA1, SAA2, and SAA3 mRNAs were expressed differentially and can be grouped into three general classes: tissues expressing all three genes, tissues expressing SAA1 and SAA3, and tissues expressing predominantly or only SAA3.

Hepatic Serum Amyloid A1 Aggravates T Cell-mediated Hepatitis by Inducing Chemokines via Toll-like Receptor 2 in Mice

“…Three SAA isoforms have been reported in mice. Saa1 and Saa2 isoforms are mainly expressed by hepatocytes, whereas the Saa3 isoform has been found to be induced in various tissues during inflammation (5,6). Under acute inflammatory conditions, such as infection, tissue damage, inflammation, and cancer, Saa1 and Saa2 are similarly induced, and serum SAA levels increase as much as 1000-fold (6).…”

“…Saa1 and Saa2 isoforms are mainly expressed by hepatocytes, whereas the Saa3 isoform has been found to be induced in various tissues during inflammation (5,6). Under acute inflammatory conditions, such as infection, tissue damage, inflammation, and cancer, Saa1 and Saa2 are similarly induced, and serum SAA levels increase as much as 1000-fold (6). Induction of the genes encoding SAA1 and SAA2 during inflammation is triggered by elevated secretion of proinflammatory cytokines, such as IL-6 and TNF-␣, into the circulation and in hepatic cells (7,8).…”

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

“…In response to a proinflammatory stimulus, the liver produces the isoforms 1.1 and 2.1, while SAA3 is mainly expressed in extrahepatic tissues [8][9][10]. More specifically, SAA3 does not contribute to circulating levels of SAA and has been related mostly to the promotion of local inflammation [9,11,12].…”

Microbial regulation of SAA3 expression in mouse colon and adipose tissue

“…11 SAA1 and SAA2 expression is restricted to the liver, intestine and kidneys whereas SAA3 is more widely expressed in mouse tissues. 13,16 In contrast, SAA1 is expressed in human adipocytes and its expression is increased in hypertrophic adipocytes from obese individuals. 17 Thus we speculated that mouse SAA3, which is upregulated in the adipose tissue of obese mice, 18 might be functionally similar to human SAA1 and perhaps represent a link between low-grade inflammation and metabolic diseases associated with obesity such as insulin resistance.…”

“…Stimulating cultured colonocytes with LPS revealed that microbial components qRT-PCR screen of adipose tissue. 11 Since intraperitoneal injections of purified lipopolysaccharide (LPS) increases adipose expression of SAA3, 13 we hypothesized that the gut microbiota may induce signaling through Toll-like receptors (Tlrs), which recognizes conserved microbial structures such as LPS.…”