Table 2.
Tissue- and stimulus-specific SAA effects in humans and rodents.
| Tissue/cell type | Model | Stimulus | SAA subtypesa |
|---|---|---|---|
| Liver | |||
| Human | HepG2 cells (234) HepG2 cells (89, 248) HepG2 cells (252) Primary hepatocytes (251) Liver tissue (98) |
IL-1β, IL-6 TNFα (10 ng/ml) IL-6 TNFα, DEX IL-1 β LPS (20–500 ng/ml) Obesity |
↑↑ SAA1, SAA2 (15–25-fold) ↔ SAA1, SAA2 ↑↑ SAA1, SAA2 (5-fold) ↔ SAA1, SAA2 ↑ SAA1 ↑↑ SAA1, SAA2 ↔ SAA1 |
| Rodent | BALB/c mice (40, 238) Swiss mice (236) C57Bl6/J mice (122, 233) Primary hepatocytes (122) Mouse fibrosis model (239) Mouse HSCs (239) C57Bl6/J mice (42) Ldlr-/-.Leiden mice (244) FVB mice (114) db/db mice (114) C57Bl6/J (121) Mouse liver (113) Mink liver (269) C57Bl6/J (209) |
LPS (50 µg) Casein (0.5 ml 10%) LPS (100 µg) LPS (100 µg) LPS (25 µg) Ccl4 (0.5 µl/g) Ccl4 (0.5 µl/g) LPS (25 µg) AgNO3 (0.5 ml 1%) Casein (0.5 ml 5%) DIO (50 weeks HFD) STZ- hyperglycemia Genetic T2D DIO (16 weeks) Amyloidosis LPS (3 mg/kg) MOG- autoimmune encephalomyelitis |
↑↑ Saa1, Saa2, Saa3 (100-fold) ↔ Saa1, Saa2 ↑↑ Saa1 ↑↑ Saa1, Saa2, Saa3 (2,000–5,000-fold) ↑↑ Saa1, Saa2, Saa3 ↑ Saa1, Saa3 (10–40-fold) ↔ Saa1, ↑ Saa3 (40-fold) ↑↑ Saa1–4 (200, 2,000, 1,000-fold) ↑↑ Saa1, Saa2 (400, 10,000-fold) ↔ Saa4, ↑ Saa1–3 (60, 1,000, 8-fold) ↔ Saa1 ↔ Saa3 ↔ Saa3 ↔ Saa3 ↓ Saa1, Saa2 ↑ Saa1 ↑↑ Saa1–2, ↔ Saa3 (10, 20-fold) |
| Adipocytes/WAT | |||
| Human | Omental and SQ adipose tissue (9) SQ adipose tissue (96, 98) MADS (253) Primary breast adipocytes (254) |
Obesity DEX, insulin Rosiglitazone Obesity Obesity → weight loss rSAA (1–30 µg/ml) DHA (50–100 µM) |
↑↑ SAA1 ↑ SAA1 (6-fold secretion) ↓ SAA1 (70% reduction in secretion) ↑ SAA1–2, SAA4 (6-fold) ↓ SAA1, SAA2 (1.6–2.2-fold) ↑ SAA1 (7-fold) ↑ SAA1 |
| Rodent | C57Bl6/J mice (42) C57Bl6/J mice (122) Ldlr-/-.Leiden mice (44) 3T3-L1 adipocytes (114) FVB mice (114) ob/ob mice (114, 121) db/db mice (114, 121) 3T3-L1 adipocytes (190) 3T3-L1 adipocytes (245) C57Bl6/J (121) 3T3-L1 adipocytes (246) 3T3-L1 adipocytes (242) Swiss Webster mice (271) |
LPS (25 µg/mouse) AgNO3 (0.5 ml 1%) Casein (0.5 ml 5%) LPS (100 µg) DIO (50 weeks HFD) TNFα, LPS Insulin, Rosi, IL-6 Hyperglycemia (25 mM) LPS (100 ng/g) STZ- hyperglycemia Obesity Genetic T2D SFA (12:0, 14:0, 16:0) Hyperglycemia (25 mM) PUFA (20:4, 20:5, 22:6) IL-1β DIO (16 weeks) LPS LPS + RAW264.7 cells rSAA (5 µg/ml) Presense of microbes |
↑↑ Saa1, Saa2, Saa3 (60, 30, 750-fold) ↔ Saa1–3 ↔ Saa1–3 ↑ Saa1 (100-fold), ↑↑ Saa3 (400-fold) ↓ Saa1 ↑↑ Saa3 ↔ Saa3 ↑ Saa3 ↑↑ Saa3 (200-fold) ↑ Saa3 ↑↑ Saa3 ↑ Saa3 (8-fold) ↑ Saa3 (2-fold) ↑ Saa3 (5-fold) ↓ Saa3 ↑ Saa3 (10,000-fold) ↑ Saa3 (11-fold) ↑ Saa1 (2-fold) ↑ Saa1 (2-fold) ↑ Saa3 (3-fold) ↑ Saa3 (10-fold), ↔ Saa1, Saa2 |
| Monocytes | |||
| Human | PBMC (250) THP-1 cells (187) U-937 cells (187) HL-60 cells (187) |
IL-1β, IL-6, TNFα LPS + DEX, or DEX LPS, DEX, IL-1, IL-6 LPS, DEX, IL-1, IL-6 |
↑ SAA2 (7-fold) ↑ SAA1 ↔ SAA1 ↔ SAA1 |
| Macrophages | |||
| Human | Coronary artery sections (18) THP-1 macrophages (187) U-937 macrophages (187) HL-60 macrophages (187) |
Atherosclerosis LPS DEX DEX LPS, DEX, IL-1, IL-6 |
↑ SAA1 ↔ SAA1 ↑ SAA1 ↑ SAA1 ↔ SAA1 |
| Rodent | BALB/c mice (40) RAW264.7 cells (246) RAW264.7 cells (271) Kupffer cells (233) Peritoneal macrophages (233) Peritoneal macrophages (113) Microglia, MDM (209) |
LPS (50 µg) LPS LPS LPS LPS Amyloidosis MOG- autoimmune encephalomyelitis |
↑↑ Saa3 (100-fold) ↔ Saa1 ↑ Saa3 ↑ Saa1 ↑ Saa1 ↑↑ Saa3 ↑ Saa3 |
| Intestine | |||
| Rodent | BALB/c mice (40) C57Bl6/J (121) CONV-R vs. GF mice (271) CONV-R vs. GF mice (278) CMT-93 colonic epithelial cells (224, 271) Mink intestine (269) |
LPS (50 µg) Casein (0.5 ml 10%) DIO (16 weeks) Presence of microbes Presence of microbes LPS LPS (3 mg/kg) |
↑↑ Saa1 (1–4-fold), Saa3 (3–25-fold) ↔ Saa1, Saa3 ↔ Saa3 ↔ Saa1, Saa2, ↑ Saa3 ↑↑ Saa1, Saa2, Saa3 (4-fold) ↑↑ Saa3 (7-fold), ↔ Saa1–2 ↑↑ Saa1 |
12:0, lauric acid; 14:0, myristic acid; 16:0, palmitic acid; 20:4, arachidonic acid; 20:5, eicosapentaenoic acid; 22:6, docosahexaenoic acid; AgNO3, silver nitrate; Ccl4, tetrachloride; CLA, conjugated linoleic acid; CONV-R, conventionally-reared; DEXv dexamethasone; db/db mice: DIO, diet-induced obesity; leptin receptor-deficient mice; DEX, dexamethasone; DHA, docohexaenoic acid; GF, germ-free; HepG2, human hepatoma cells; HSC, hepatic stellate cells; IL-1β, interleukin 1 beta; IL-6, interleukin 6; LPS, lipopolysaccharide; MDM, monocyte-derived macrophage; MOG, myelin oligodendrocyte glycoprotein; ob/ob mice, leptin-deficient mice; PBMCs, peripheral blood mononuclear cells; PUFA, polyunsaturated fatty acids; rSAA, recombinant SAA; SFA, short chain fatty acids; SQ, subcutaneous; STZ, streptozotocin; T2D, type 2 diabetes; TNFα, tumor necrosis factor alpha; WAT, white adipose tissue; ↑, modest increase; ↑↑, robust increase; ↔, no change.
Fold-mRNA expression, unless otherwise indicated.