0000000000669194
AUTHOR
Ana María Vicente
Beneficial effects of heme oxygenase-1 up-regulation in the development of experimental inflammation induced by zymosan.
Heme oxygenase-1 (HO-1) is part of the integrated response to oxidative stress. This enzyme may exert anti-inflammatory effects in some animal models, although the precise mechanisms are not fully understood. We have examined the role of HO-1 in the inflammatory response induced by zymosan in the mouse air pouch. Zymosan administration induced HO-1 protein expression in leukocytes migrating to exudates, with maximal levels in the late phase of this response (24-48 h). This was accompanied by ferritin induction and bilirubin accumulation, indicating that this enzyme is active in our model. HO-1 expression by zymosan treatment was partly reduced by aminoguanidine, suggesting the participation…
Participation of Heme Oxygenase-1 in a Model of Acute Inflammation
In this study, the role of heme oxygenase-1 (HO-1) in the inflammatory response elicited by zymosan in the mouse air pouch model has been examined. This response is characterized by a time-dependent increase in HO-1 expression in the leukocytes migrating into the exudates. At 24–48 h maximal HO-1 expression was accompanied by reduced cyclooxygenase-2 (COX-2) and nitric oxide synthase-2 (NOS-2) expression as well as low levels of inflammatory mediators. Hemin administration into the air pouch caused an elevation of HO-1 protein and bilirubin levels induced by zymosan with inhibition of COX-2 expression. In mouse peritoneal macrophages from hemin-injected mice, we also observed an increased …
Heme oxygenase-1 induction by nitric oxide in RAW 264.7 macrophages is upregulated by a cyclo-oxygenase-2 inhibitor.
Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1) protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO) induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a significant potentiation in the presence of SC58125, which did not modify HO-1 mRNA stability. The induction of HO-1 by NO and its potentiation by anti-inflammatory agents may play a role in inflammatory and immune responses.
Heme oxygenase-1 induction and regulation in unstimulated mouse peritoneal macrophages
Heme oxygenase-1 (HO-1) is a stress protein induced by a variety of stimuli in inflammatory cells. This study was set up to investigate the induction of this protein in unstimulated macrophages. Resident mouse peritoneal macrophages purified by adhesion and cultured in basal conditions strongly induced HO-1 in a time-dependent manner, with a peak at 20 hr. At the same time, low levels of nitrite accumulated in the culture medium and expression of nitric oxide synthase-2 (NOS-2) and NOS-3 protein was detected. Inhibition of NO production and/or NOS expression by incubating macrophages with different drugs inhibiting NOS activity or modulating the redox state of the cell, such as N-acetylcyst…
Modulation of haem oxygenase-1 expression by nitric oxide and leukotrienes in zymosan-activated macrophages
Phagocytosis of unopsonized zymosan by RAW 264.7 macrophages upregulated protein expression of haem oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) in a time- and concentration-dependent manner. In the presence of zymosan, exogenous prostaglandin E(2) (PGE(2)) did not exert significant effects on the expression of these three enzymes. In contrast, exogenous leukotriene B(4) (LTB(4)) and LTC(4) in the nanomolar range inhibited HO-1 and iNOS expression, as well as nitrite accumulation. The COX inhibitors indomethacin and NS398 weakly inhibited HO-1 expression but had no effect on iNOS and COX-2 expression or nitrite. In contrast, the 5-lipoxygenase (5-…
Role of nuclear factor-κB and heme oxygenase-1 in the mechanism of action of an anti-inflammatory chalcone derivative in RAW 264.7 cells
The synthetic chalcone 3',4',5',3,4,5-hexamethoxy-chalcone (CH) is an anti-inflammatory compound able to reduce nitric oxide (NO) production by inhibition of inducible NO synthase protein synthesis. In this work, we have studied the mechanisms of action of this compound. CH (10-30 microm) prevents the overproduction of NO in RAW 264.7 macrophages stimulated with lipopolysaccharide (1 microg ml(-1)) due to the inhibition of nuclear factor kappaB (NF-kappaB) activation. We have shown that treatment of cells with CH results in diminished degradation of the NF-kappaB-IkappaB complex leading to inhibition of NF-kappaB translocation into the nucleus, DNA binding and transcriptional activity. We a…