The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects

Osuji, Faustina Nkechi; Onyenekwe, Charles Chinedum; Ahaneku, Joseph Eberendu; Ukibe, Nkiruka Rose

doi:10.1186/s12929-018-0490-9

Cited by 99 publications

(83 citation statements)

References 29 publications

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“…One of these studies showed that upon Schistosoma mansoni infection, the IL‐4 cytokine upregulates miR‐182 expression Th2‐Treg cells, thereby suppressing IL‐2 secretion of the Th1 response . Another found the IL‐4 cytokine in significantly higher levels in HIV mono‐infected subjects . In the present study, there was no correlation between miR‐182 and cytokines.…”

Section: Discussioncontrasting

confidence: 45%

Higher levels of TNF and IL‐4 cytokines and low miR‐182 expression in visceral leishmaniasis‐HIV co‐infected patients

Júnior

Justo

Santos

et al. 2020

Parasite Immunology

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Aims The aim of the present study was to assess serum cytokine and miRNA expression in visceral leishmaniasis‐HIV (VL‐HIV) co‐infection and HIV mono‐infection. Methods and results We analysed 113 serum samples from HIV patients in areas endemic for leishmaniasis. The diagnosis of VL was confirmed in 65 of these 113 samples. The VL‐HIV and HIV groups presented significant differences regarding haemoglobin level (P < .0001), lymphocyte count (P = .0444), white blood cell count (P = .0108), weight loss (P = .0310), HIV load (P < .0001) and CD4+ T‐lymphocytes count (P = .0003). Levels of IL‐6 and IL‐10, IFN‐γ and IL‐6, IFN‐γ and IL‐10, TNF and IL‐2 were positively correlated in VL‐HIV co‐infection, indicating higher serum levels of TNF and IL‐4 (P < .0001). In addition, miR‐182 expression was found to be significantly higher in HIV (P = .009), miR‐210 exhibited no statistically significant difference between groups, and nonexpression of miR‐122 was found in both groups. Conclusion Together, TNF, IL‐4 and miR‐182 may represent circulatory biomarkers of VL‐HIV co‐infection.

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Section: Discussioncontrasting

confidence: 45%

Higher levels of TNF and IL‐4 cytokines and low miR‐182 expression in visceral leishmaniasis‐HIV co‐infected patients

Júnior

Justo

Santos

et al. 2020

Parasite Immunology

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“…The abnormally hyper activation of immune system has been widely reported in viral infection including HIV-1 and significantly correlated with the severity of the disease [ 40 , 41 ]. Previously, it has been shown that HIV-1 Tat induces the expression of pro-inflammatory molecules like IL-6 and IL-8 in both human monocytes and dendritic cells of HIV-1 patients [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

Novel role of mortalin in attenuating HIV-1 Tat-mediated astrogliosis

Priyanka

Wadhwa

Chaudhuri

et al. 2020

J Neuroinflammation

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Background In human immunodeficiency virus-1 (HIV-1) infection, activation of astrocytes induces imbalance in physiological functions due to perturbed astrocytic functions that unleashes toxicity on neurons. This leads to inflammatory response finally culminating into neurocognitive dysfunction. In neuroAIDS, HIV-1 protein, transactivator of transcription (Tat) is detected in the cerebrospinal fluid of infected patients. Mortalin, a multifunctional protein, has anti-inflammatory role following its activation in various stress conditions. Recent studies demonstrate downregulation of mortalin in neurodegenerative diseases. Here, we explored the mechanisms of mortalin in modulating HIV-1 Tat-mediated neuroinflammation. Methods Expression of mortalin in autopsy section in normal and diseased individuals were examined using immunohistochemistry. To decipher the role of mortalin in HIV-1 Tat-induced activation, human fetal brain-derived astrocytes were transiently transfected with Tat and mortalin using expression vectors. HIV-1 Tat-mediated damage was analyzed using RT-PCR and western blotting. Modulatory role of mortalin was examined by coexpressing it with Tat, followed by examination of mitochondrial morphodynamics using biochemical assay and confocal and electron microscopy. Extracellular ATP release was monitored using luciferase assay. Neuroinflammation in astrocytes was examined using flow cytometry, dye based study, immunocytochemistry, immunoprecipitation, and western blotting. Indirect neuronal damage was also analyzed. Results HIV-1 Tat downregulates the expression of mortalin in astrocytes, and this is corroborated with autopsy sections of HIV-1 patients. We found that overexpression of mortalin with Tat reduced inflammation and also rescued astrocytic-mediated neuronal death. Using bioinformatics, we discovered that binding of mortalin with Tat leads to Tat degradation and rescues the cell from neuroinflammation. Blocking of proteosomal pathway rescued the Tat degradation and revealed the ubiquitination of Tat. Conclusion Overall, our data demonstrated the protective role of mortalin in combating HIV-1 Tat-mediated damage. We also showed that mortalin could degrade Tat through direct binding with HIV-1 Tat. Overexpression of mortalin in the presence of Tat could significantly reduce cytotoxic effects of Tat in astrocytes. Indirect neuronal death was also found to be rescued. Our in vitro findings were validated as we found attenuated expression of mortalin in the autopsy sections of HIV-1 patients.

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“…Fewer CD4-positive cells may prevent IL-2 and IFN-γ secretion, 26 even after a lengthy period of antiretroviral therapy. 27 Hence, it is possible that lower levels of pro-inflammatory cytokines, particularly IFN-γ, can affect the tumor microenvironment and lead to a decrease in PD-L1 expression in tumor cells or immune cells of HIV patients. In addition, some studies have demonstrated that several signalling genes, such as NF-κB, MAPK, and JAK/STAT, are also down-regulated after ART.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer

et al. 2020

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Background: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) axis may represent a target for cervical cancer; however, it is poorly understood in human immunodeﬁciency virus (HIV)-infected patients. Methods: We evaluated HIV-positive ( n = 42) and HIV-negative ( n = 110) women with locally advanced cervical cancer regarding their PD-L1 expression, determined by combined positive score (CPS) ⩾ 1 and tumor proportion score (TPS) ⩾ 25%, and PD-L1 copy number alterations, assessed by fluorescence in situ hybridization. Results: Regardless of HIV status, 84.9% and 44.8% of cases were PD-L1-positive according to CPS ⩾ 1 and TPS ⩾ 25%. Per CPS ⩾ 1, PD-L1 positive rate was similar between HIV-positive and HIV-negative women, whereas a significant difference was seen per TPS ⩾ 25%. Tumor size and parametrial invasion were correlated with PD-L1 positivity in HIV-negative women, whereas anti-retroviral therapy (ART) was correlated with TPS < 25%. Low CD4-positive cell counts were associated with CPS < 1 in HIV-positive women. No significant difference was observed in PD-L1 copy number status between HIV-positive and HIV-negative women. PD-L1 amplification and polysomy were independently associated with TPS ⩾ 25%, whereas the presence of parametrial invasion was independently associated with CPS ⩾ 1. Cancer stage and PD-L1 amplification were identified as independent predictors of recurrence-free survival [hazard ratio (HR) = 2.40 (1.32–4.36) and HR = 5.33 (1.94–14.61)] and cancer-specific survival [HR = 13.62 (5.1–36.38) and HR = 3.53 (1.43–8.69)]. PD-L1 polysomy was an independent predictor of locoregional recurrence-free survival [HR = 3.27 (1.27–8.41)]. HIV status and PD-L1 expression (CPS ⩾ 1 or TPS ⩾ 25%) were not associated with poor patient outcomes. Conclusion: PD-L1 amplification and polysomy are the strongest drivers of PD-L1 expression in cervical cancer, and could represent prognostic biomarkers for anti-PD-1/PD-L1 therapy. Cervical cancer biology may be modulated by HIV infection, CD4-positive cells, and HIV treatments.

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The effects of highly active antiretroviral therapy on the serum levels of pro-inflammatory and anti-inflammatory cytokines in HIV infected subjects

Cited by 99 publications

References 29 publications

Higher levels of TNF and IL‐4 cytokines and low miR‐182 expression in visceral leishmaniasis‐HIV co‐infected patients

Higher levels of TNF and IL‐4 cytokines and low miR‐182 expression in visceral leishmaniasis‐HIV co‐infected patients

Novel role of mortalin in attenuating HIV-1 Tat-mediated astrogliosis

PD-L1 protein expression and copy number gains in HIV-positive locally advanced cervical cancer

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