Cytokine regulation of acute and chronic HIV infection in vitro : from cell lines to primary mononuclear cells

1994 ◽  
Vol 145 (8-9) ◽  
pp. 578-582 ◽  
Author(s):  
G. Poli ◽  
A.L. Kinter ◽  
E. Vicenzi ◽  
A.S. Fauci
Keyword(s):  
Hiv Infection ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Cytokine Regulation ◽  
Chronic Hiv Infection

scholarly journals Buprenorphine Increases HIV-1 Infection In Vitro but Does Not Reactivate HIV-1 from Latency

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1472
Author(s):  
Germán Gustavo Gornalusse ◽  
Lucia N. Vojtech ◽  
Claire N. Levy ◽  
Sean M. Hughes ◽  
Yeseul Kim ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Hiv Infection ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Receptor Expression ◽  
People Living With Hiv ◽  
Peripheral Blood Mononuclear ◽  
In Vitro Susceptibility ◽  
Hiv 1

Background: medication-assisted treatment (MAT) with buprenorphine is now widely prescribed to treat addiction to heroin and other illicit opioids. There is some evidence that illicit opioids enhance HIV-1 replication and accelerate AIDS pathogenesis, but the effect of buprenorphine is unknown. Methods: we obtained peripheral blood mononuclear cells (PBMCs) from healthy volunteers and cultured them in the presence of morphine, buprenorphine, or methadone. We infected the cells with a replication-competent CCR5-tropic HIV-1 reporter virus encoding a secreted nanoluciferase gene, and measured infection by luciferase activity in the supernatants over time. We also surveyed opioid receptor expression in PBMC, genital epithelial cells and other leukocytes by qPCR and western blotting. Reactivation from latency was assessed in J-Lat 11.1 and U1 cell lines. Results: we did not detect expression of classical opioid receptors in leukocytes, but did find nociception/orphanin FQ receptor (NOP) expression in blood and vaginal lymphocytes as well as genital epithelial cells. In PBMCs, we found that at physiological doses, morphine, and methadone had a variable or no effect on HIV infection, but buprenorphine treatment significantly increased HIV-1 infectivity (median: 8.797-fold increase with 20 nM buprenorphine, eight experiments, range: 3.570–691.9, p = 0.0078). Using latently infected cell lines, we did not detect reactivation of latent HIV following treatment with any of the opioid drugs. Conclusions: our results suggest that buprenorphine, in contrast to morphine or methadone, increases the in vitro susceptibility of leukocytes to HIV-1 infection but has no effect on in vitro HIV reactivation. These findings contribute to our understanding how opioids, including those used for MAT, affect HIV infection and reactivation, and can help to inform the choice of MAT for people living with HIV or who are at risk of HIV infection.

Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length

2021 ◽  
Author(s):  
Marieke Raffenberg ◽  
Tanja Engel ◽  
Isabella C Schoepf ◽  
Neeltje A Kootstra ◽  
Peter Reiss ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Telomere Length ◽  
Antiretroviral Treatment ◽  
Mononuclear Cells ◽  
Multivariable Analysis ◽  
Limited Effect ◽  
Peripheral Blood Mononuclear ◽  
Primary Hiv Infection ◽  
Hiv Seroconversion ◽  
Chronic Hiv Infection

Abstract Background Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI). Methods We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. Results In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables. Discussion In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

Flavopiridol Induces Apoptosis in Chronic Lymphocytic Leukemia Cells Via Activation of Caspase-3 Without Evidence of bcl-2 Modulation or Dependence on Functional p53

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3804-3816 ◽  
Author(s):  
John C. Byrd ◽  
Charlotte Shinn ◽  
Jamie K. Waselenko ◽  
Ephraim J. Fuchs ◽  
Teresa A. Lehman ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Lines ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
P53 Protein ◽  
Lymphocytic Leukemia ◽  
Vitro Activity ◽  
Interleukin 4 ◽  
In Vitro Activity

Abstract Flavopiridol has been reported to induce apoptosis in lymphoid cell lines via downregulation of bcl-2. The in vitro activity of flavopiridol against human chronic lymphocytic leukemia (CLL) cells and potential mechanisms of action for inducing cytotoxicity were studied. The in vitro viability of mononuclear cells from CLL patients (n = 11) was reduced by 50% at 4 hours, 24 hours, and 4 days at a flavopiridol concentration of 1.15 μmol/L (95% confidence interval [CI] ±0.31), 0.18 μmol/L (95% CI ±0.04), and 0.16 μmol/L (95% CI ±0.04), respectively. Loss of viability in human CLL cells correlated with early induction of apoptosis. Exposure of CLL cells to 0.18 μmol/L of flavopiridol resulted in both decreased expression of p53 protein and cleavage of the caspase-3 zymogen 32-kD protein with the appearance of its 20-kD subunit. Contrasting observations of others in tumor cell lines, flavopiridol cytotoxicity in CLL cells did not correlate with changes in bcl-2 protein expression alterations. We evaluated flavopiridol’s dependence on intact p53 by exposing splenocytes from wild-type (p53+/+) and p53 null (p53−/−) mice that demonstrated no preferential cytotoxicity as compared with a marked differential with F-ara-a and radiation. Incubation of CLL cells with antiapoptotic cytokine interleukin-4 (IL-4) did not alter the LC50 of flavopiridol, as compared with a marked elevation noted with F-ara-a in the majority of patients tested. These data demonstrate that flavopiridol has significant in vitro activity against human CLL cells through activation of caspase-3, which appears to occur independently of bcl-2 modulation, the presence of IL-4, or p53 status. Such findings strongly support the early introduction of flavopiridol into clinical trials for patients with B-CLL.

scholarly journals Pivotal role of M-DC8+ monocytes from viremic HIV-infected patients in TNFα overproduction in response to microbial products

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2259-2268 ◽  
Author(s):  
Charles-Antoine Dutertre ◽  
Sonia Amraoui ◽  
Annalisa DeRosa ◽  
Jean-Pierre Jourdain ◽  
Lene Vimeux ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Intestinal Epithelial ◽  
Color Flow ◽  
Gm Csf ◽  
Cell Counts

Abstract HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)+ and CD1c (BDCA-1)+ dendritic cell counts were reduced. Conversely, CD14+CD16++ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14++CD16−M-DC8− monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppressed patients. M-DC8+ monocytes were mostly responsible for this overproduction. Moreover, M-DC8+ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8+ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression.

scholarly journals Fucoxanthin, A Carotenoid Derived from Phaeodactylum tricornutum Exerts Antiproliferative and Antioxidant Activities In Vitro

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 183 ◽  
Author(s):  
Ulrike Neumann ◽  
Felix Derwenskus ◽  
Verena Flaiz Flister ◽  
Ulrike Schmid-Staiger ◽  
Thomas Hirth ◽  
...  
Keyword(s):  
Health Effects ◽  
Cell Lines ◽  
Metabolic Activity ◽  
Phaeodactylum Tricornutum ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Antioxidant Activities ◽  
Fold Increase ◽  
Anti Inflammatory

Microalgae contain a multitude of nutrients and can be grown sustainably. Fucoxanthin, a carotenoid from Phaeodactylum tricornutum, could have beneficial health effects. Therefore, we investigated the anti-inflammatory, antioxidative and antiproliferative effects of fucoxanthin derived from this diatom in vitro. The effects of purified fucoxanthin on metabolic activity were assessed in blood mononuclear cells and different cell lines. In cell lines, caspase 3/7 activity was also analyzed. Nitrogen monoxide release and mRNA-expression of proinflammatory cytokines were measured. For antioxidant assays, cell free assays were conducted. Additionally, the antioxidant effect in neutrophils was quantified and glutathione was determined in HeLa cells. The results show that neither did fucoxanthin have anti-inflammatory properties nor did it exert cytotoxic effects on mononuclear cells. However, the metabolic activity of cell lines was decreased up to 58% and fucoxanthin increased the caspase 3/7 activity up to 4.6-fold. Additionally, dose-dependent antioxidant effects were detected, resulting in a 63% decrease in chemiluminescence in blood neutrophils and a 3.3-fold increase in the ratio of reduced to oxidized glutathione. Our studies show that fucoxanthin possesses antiproliferative and antioxidant activities in vitro. Hence, this carotenoid or the whole microalgae P. tricornutum could be considered as a food or nutraceutical in human nutrition, showcasing beneficial health effects.

scholarly journals MDL 74,968, a new acyclonucleotide analog: activity against human immunodeficiency virus in vitro and in the hu-PBL-SCID.beige mouse model of infection.

1996 ◽  
Vol 40 (5) ◽  
pp. 1072-1077 ◽  
Author(s):  
C G Bridges ◽  
D L Taylor ◽  
P S Ahmed ◽  
T M Brennan ◽  
J M Hornsperger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Placebo Control ◽  
Intravenous Route ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Orally Bioavailable

The novel acyclonucleotide derivative of guanine, 9-[2-methylidene-3-(phosphonomethoxy)propyl] guanine (MDL 74,968), had antiviral activity comparable to those of 9-(2-phosphonomethoxyethyl) adenine (PMEA) and 2',3'-dideoxyinosine against laboratory strains of both human immunodeficiency virus (HIV) types 1 and 2 cultured in MT-4 cells and several clinical HIV isolates cultured in human peripheral blood mononuclear cells (PBMCs). MDL 74,968 was at least fourfold less toxic than PMEA to MT-4 cells or PBMCs, thereby producing a more favorable in vitro selectivity index for the former compound. Studies of acute toxicity in CD-1 mice showed that MDL 74,968 was not toxic at doses of 1,600 mg/kg of body weight via the intraperitoneal route or at doses of 500 mg/kg via the intravenous route. Furthermore, no adverse effects of MDL 74,968 were apparent when mice were treated at doses of 200 mg/kg twice daily for 5 days. Treatment by continuous subcutaneous infusion of MDL 74,968 or PMEA at the daily dose of 20 mg/kg in the hu-PBL-SCID.beige murine model of HIV infection significantly reduced the severity of infection compared with that in placebo-treated controls. Quantitation of virus recovery by endpoint titration of spleen cells in coculture with mitogen-activated PBMCs demonstrated that MDL 74,968 as well as PMEA significantly reduced the amount of virus (P < 0.02). Moreover, by using DNA extracted from spleens, the mean HIV:HLA PCR product ratio, which takes into account individual variation in immune system reconstitution, were 0.50 and 0.40 for MDL 74,968 and PMEA treatments, respectively, whereas animals receiving the placebo control had significantly higher levels of HIV proviral DNA (mean 0.78; P < 0.02). Taken together, these promising findings suggest that an orally bioavailable prodrug of MDL 74,968 should be developed for the treatment of HIV infection.

scholarly journals Verotoxin A Subunit Protects Lymphocytes and T Cell Lines against X4 HIV Infection in Vitro

Toxins ◽  
2012 ◽  
Vol 4 (12) ◽  
pp. 1517-1534 ◽  
Author(s):  
Pei Shi ◽  
Beth Binnington ◽  
Darinka Sakac ◽  
Yulia Katsman ◽  
Stephanie Ramkumar ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Lines ◽  
A Subunit ◽  
T Cell Lines

Pioglitazone Inhibits the Growth of Human Leukemic Cell Lines and Primary Leukemic Cells in Vitro.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4493-4493 ◽  
Author(s):  
Yoshihiro Hatta ◽  
Minoru Saiki ◽  
Yuko Enomoto ◽  
Shin Aizawa ◽  
Umihiko Sawada ◽  
...  
Keyword(s):  
Cell Lines ◽  
Colony Formation ◽  
Mononuclear Cells ◽  
Hematopoietic Cells ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Peroxisome Proliferator ◽  
Leukemic Cell Lines ◽  
Ppar Γ

Abstract Troglitazone and pioglitazone are one of thiazolidinediones that are high affinity ligand for the nuclear receptor called peroxisome proliferator-activated receptor gamma (PPAR-γ). Troglitazone is a potent inhibitor of clonogenic growth of acute myeloid leukemia cells when combined with a retinoid. However, the effect of pioglitazone to neoplastic cells and normal hematopoietic cells has not been studied yet. Adult T-cell leukemia (ATL), prevalent in western Japan, is a highly aggressive malignancy of mature T lymphocyte. Therefore, we studied antitumor effect of pioglitazone against leukemic cells including ATL as well as normal hematopoietic cells. With 300 μM of pioglitazone, colony formation of ATL cell lines (MT1, MT2, F6T, OKM3T, and Su9T01) was completely inhibited. Colony formation of HUT102, another ATL cell line, was 12 % compared to untreated control. Clonogenic cells of other leukemic cell lines (K562, HL60, U937, HEL, CEM, and NALM1) was also inhibited to 0–30% of control. Colony formation of primary leukemic cells from 5 AML patients was decreased to 15 %. However, normal hematopoietic cells were weakly inhibited with 300 μM pioglitazone; 77 % of CFU-GM, 70 % of CFU-E, and 33 % of BFU-E survived. Cell cycle analysis showed that pioglitazone decreased the ratio of G2/M phase in HL60 cells, suggesting the inhibition of cell division. By Western blotting, PPAR-γ protein level was similar in all leukemic cells and normal bone marrow mononuclear cells. Taken together, pioglitazone effectively eliminate leukemic cells and could be used as an antitumor agent in vivo.

Sign in / Sign up

Export Citation Format

Share Document