LPS induces cell death in macrophages through three main mechanisms:
1. LPS induces nitrite production and apoptosis in macrophages through autocrine production of TNF-α.
2. LPS-induced apoptosis reaches a plateau at around 6 hours, while NO production requires 12-24 hours.
3. Early apoptosis is reduced by iNOS inhibitors but not by lack of TNF receptors, while late apoptosis relies on NO production regardless of TNF receptor signaling.
LPS induces cell death in macrophages through three main mechanisms:
1. LPS induces nitrite production and apoptosis in macrophages through autocrine production of TNF-α.
2. LPS-induced apoptosis reaches a plateau at around 6 hours, while NO production requires 12-24 hours.
3. Early apoptosis is reduced by iNOS inhibitors but not by lack of TNF receptors, while late apoptosis relies on NO production regardless of TNF receptor signaling.
LPS induces cell death in macrophages through three main mechanisms:
1. LPS induces nitrite production and apoptosis in macrophages through autocrine production of TNF-α.
2. LPS-induced apoptosis reaches a plateau at around 6 hours, while NO production requires 12-24 hours.
3. Early apoptosis is reduced by iNOS inhibitors but not by lack of TNF receptors, while late apoptosis relies on NO production regardless of TNF receptor signaling.
LPS induced nitrite production and LPS induces apoptosis
in macrophages mostly through the autocrine production of TNF-α. LPS induces
apoptosis in bone marrow-derived macrophages (BMDM). LPS-induced apoptosis reached a plateau at about 6 hours of stimulation, whereas the production of NO by the inducible NO-synthase (iNOS) required between 12 and 24 hours. Furthermore, LPS-induced early apoptosis was only moderately reduced in the presence of an inhibitor of iNOS or when using macrophages from iNOS -/-mice. In contrast, early apoptosis was paralleled by the rapid secretion of TNF and was almost absent in macrophages from mice deficient for one (p55) or both (p55 and p75) TNF-receptors. During the late phase of apoptosis (12-24 hours) NO significantly contributed to the death of macrophages even in the absence of TNF-receptor signaling. NO-mediated cell death, but not apoptosis induced by TNF, correlated with the induction of p53 and Bax genes. Thus, LPS-induced apoptosis results from 2 independent mechanisms: first and predominantly, through the autocrine secretion of TNF- (early apoptotic events), and second, through the production of NO (late phase of apoptosis). Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone. The effects of dexamethasone are frequently seen within a day and last for about three days. Dexamethasone has been investigated in the RECOVERY trial in the treatment of hospitalised patients with confirmed or suspected SARS-CoV-2 infection and severe disease. The results show that dexamethasone reduce 28-day mortality substantially among patients who received oxygen or ventilation at the time of randomisation.