Synergistic regulation of the acute phase protein SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines.
SIP24/24p3 is a secreted murine acute phase protein which has been speculated to play an anti-inflammatory role in vivo. Recently SIP24/24p3 has been found to be able to specifically induce apoptosis in leukocytes. By using (35)S metabolic labeling method, we studied the regulation of SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines IL-6 and TNF-alpha in cultured Balb/c 3T3 and BNL cells. The following results were observed: (1) dexamethasone induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells, the induction was more significant in BNL cells; (2) dexamethasone and IL-6 synergistically induced the expression of SIP24/24p3 in both Balb/c 3T3 and BNL cells; (3) in Balb/c 3T3 cells dexamethasone and TNF-alpha acted synergistically to induce the expression of SIP24/24p3, whereas in BNL cells dexamethasone and TNF-alpha induced the expression of SIP24/24p3 in an additive manner; (4) dexamethasone and IL-6/TNF-alpha acted synergistically in Balb/c 3T3 cells and additively in BNL cells to induce the expression of SIP24/24p3. The inducibility of SIP24/24p3 by multiple factors will help to explain its highly specific expression in vivo. The difference in the expression patterns of SIP24/24p3 in different cell types is also suggestive to its expression and regulation in hepatic and extrahepatic tissues. Finally, the fact that SIP24/24p3 protein can be induced by both pro-inflammatory as well as anti-inflammatory factors is indicative of the important role of SIP24/24p3 in the entire acute phase response process.
Liu
Quan-Sheng
QS
Department of Immunology and Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University.
Nilsen-Hamilton
Marit
M
Xiong
Si-Dong
SD
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D041702:BALB 3T3 Cells; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000494:pharmacology*; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D008807:Mice, Inbred BALB C; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D016207:Cytokines; D015850:Interleukin-6; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C071332:Lcn2 protein, mouse; D003907:Dexamethasone