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Dexamethasone modifies the functional responses of the granulocytic differentiating HL-60 cells.

ABSTRACT: We have studied the effect of dexamethasone on the granulocytic differentiation of the human promyelocytic cell line HL-60 induced by treatment with retinoic acid (RA) or dimethyl sulphoxide (DMSO). Dexamethasone potentiated the immunophenotypic and functional parameters associated with the granulocytic differentiation induced by RA, including changes in CD11b and CD71 expression, inhibition of cell proliferation, enhancement of secretory and oxidative responses and increase of the phospholipase C (PLC), phospholipase A2 (PLA2) and phospholipase D (PLD) activities. However, dexamethasone had selective effects on several parameters of DMSO-induced cell differentiation. Dexamethasone inhibited the DMSO-induced increase of CD11b cell surface expression as well as the oxidative response and PLD activation triggered by 4 beta-phorbol 12-myristate 13-acetate. Nevertheless, dexamethasone potentiated the receptor-mediated PLC activation and the receptor-mediated secretory and oxidative responses in DMSO-treated cells. Unlike RA-treated HL-60 cells, the DMSO-treated cells contained high values of activatable PLA2 activity which were not affected by dexamethasone. Thus dexamethasone affected differently functional parameters and effector systems of granulocytic HL-60 cells, depending on the differentiation agent used. Dexamethasone by itself did not induce HL-60 cell differentiation, but enhanced the receptor- and non-receptor-mediated secretory responses and induced the appearance of stimulated PLA2 activity in undifferentiated HL-60 cells. These data provide evidence for the selective modulation of functional responses by dexamethasone through alterations in signalling processes.

SUBMITTER: Collado-Escobar D

PROVIDER: S-EPMC1138307 | biostudies-other | 1994 Apr

REPOSITORIES: biostudies-other

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KN-62 analogues as potent differentiating agents of HL-60 cells.

Project description:KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances the terminal differentiation of retinoic acid sensitive human myeloid leukemia cell lines. In an effort to identify additional CaMK inhibitors that exhibit more potent activity in triggering leukemia cell differentiation, we synthesized 45 analogues of KN-62 and determined their ability to induce HL-60 cell differentiation. Sixteen of these novel analogues exhibited significant differentiation-inducing activity, and one analogue, AS-004, was five times more potent than KN-62 in inhibiting proliferation and inducing differentiation of HL-60 cells. Such KN-62 analogues and/or related compounds may prove useful in treating promyelocytic leukemia.

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TNF-α Differentially Regulates Cell Cycle Genes in Promyelocytic and Granulocytic HL-60/S4 Cells.

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Project description:Ehrlichia spp. from human and equine sources in the northeastern Unites States were detected by PCR, isolated, and propagated in the HL-60 promyelocytic leukemia cell line. Growth of Ehrlichia from both equine and human sources was enhanced by addition of retinoic acid, which causes granulocytic differentiation of the HL-60 cells. DNA sequencing of a portion of the 16S rDNA gene supported the hypothesis that the same pathogen was responsible for both equine and human granulocytic ehrlichiosis.

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Dexamethasone Attenuates Oncostatin M Production via Suppressing of PI3K/Akt/NF-κB Signaling in Neutrophil-like Differentiated HL-60 Cells.

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Project description:Cyclo-oxygenase (COX) production in human promyelocytic leukaemia (HL-60) cells was studied during monocytic differentiation induced by 1 alpha, 25-dihydroxyvitamin D3 (24 nM; 3 days) or phorbol 12-myristate 13-acetate (100 nM; 1 day), or during granulocytic differentiation induced by retinoic acid (1 microns; 4 days). Undifferentiated or differentiated HL-60 cells were labelled with [35S]methionine, and membrane-bound COX was solubilized and quantified by SDS/PAGE. Immunoprecipitated 35S-labelled COX from cells induced to differentiate into monocytic or granulocytic lineage were clearly detected on the autoradiograms as a protein of approx. 70 kDa molecular size, whereas only a very faint COX band was detected in untreated HL-60 cells. During both monocytic and granulocytic differentiation, COX activity (measured by the conversion of exogenous arachidonic acid into prostaglandin E2) was dramatically increased. In addition, thromboxane synthesis was preferentially enhanced during monocytic differentiation. HL-60 cells, induced to differentiate into the monocytic or granulocytic lineage, provide a useful tool to investigate the cellular mechanisms involved in regulation of the synthesis of individual prostanoid-metabolizing enzymes.

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Resveratrol induces autophagy-dependent apoptosis in HL-60 cells.

Project description:BACKGROUND:All known mechanisms of apoptosis induced by resveratrol act through cell cycle arrest and changes in mitochondrial membrane potential. It is currently unknown whether resveratrol-induced apoptosis is associated with other physiological processes, such as autophagy. METHODS:Apoptosis-related markers involved in the intrinsic and extrinsic apoptotic pathways, and autophagic markers were detected by using western blotting and immunofluorescence. Mitochondrial membrane potential was assayed by flow cytometry. Pharmaceutical or genetic inhibition of autophagy involved were carried by 3- methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. Differences between two values were tested by Student's unpaired t test. RESULTS:We show that resveratrol-induced apoptosis occurs through both the intrinsic and extrinsic apoptotic pathways. Mitochondrial membrane potential and apoptosis-related markers, such as an increased Bax/Bcl-2 ratio, and cleaved forms of caspase-8 and caspase-3, arise following resveratrol addition. Moreover, we find that resveratrol increases both the levels of microtubule-associated protein 1 light chain 3-II and the number of autophagosomes, and further demonstrate that resveratrol-induced autophagy depends on the LKB1-AMPK-mTOR pathway. We next reveal that some apoptosis-related markers induced by resveratrol are further attenuated by the inhibition of autophagy with 3-methyladenine or knockdown of autophagy-related (Atg) genes by siRNA. CONCLUSIONS:These results suggest that resveratrol induced apoptotic cell death of HL-60 cells depends on the autophagy activated through both the LKB1-AMPK and PI3K/AKT-regulated mTOR signaling pathways.

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Project description:The human leukemia cell line (HL-60) is an alternative to primary neutrophils in research studies. However, because HL-60 cells proliferate in an incompletely differentiated state, they must undergo differentiation before they acquire the functional properties of neutrophils. Here we provide evidence of swarming and chemotaxis in differentiated HL-60 neutrophil-like cells (dHL-60) using precise microfluidic assays. We found that dimethyl sulfoxide differentiated HL-60 cells (DdHL-60) have a larger size, increased length, and lower ability to squeeze through narrow channels compared to primary neutrophils. They migrate through tapered microfluidic channels slower than primary neutrophils, but faster than HL-60s differentiated by other protocols, e.g., using all-trans retinoic acid. We found that dHL-60 can swarm toward zymosan particle clusters, though they display disorganized migratory patterns and produce swarms of smaller size compared to primary neutrophils.

| S-EPMC7804120 | biostudies-literature

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