Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Dokur, Madhavi; Boyadjieva, Nadka; Sarkar, Dipak K.

doi:10.1111/j.1530-0277.2003.tb04403.x

Cited by 6 publications

(10 citation statements)

References 48 publications

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“…Lipopolysaccharide did not increase granzyme B mRNA levels in ethanol-fed animals. Consistent with the previous findings (Boyadjieva et al, 2001;Dokur et al, 2003), ethanol feeding reduced ( po0.05) the basal levels of perforin and granzyme B mRNAs in the spleen.…”

Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spsupporting

confidence: 92%

“…We have previously shown that ethanol consumption for 2 weeks suppressed basal splenic NK cell cytolytic activity (Boyadjieva et al, 2001;Dokur et al, 2003). Consistent with these findings, the data shown in Fig.…”

Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spsupporting

confidence: 89%

“…Perforin and granzyme B are 2 cytotoxic factors that are known to regulate the NK cell cytolytic activity (Podack et al, 1991;Shresta et al, 1995). We have previously shown that chronic ethanol consumption decreased the basal mRNA and protein levels of perforin and granzyme B in the spleen (Dokur et al, 2003). We determined whether ethanol consumption also affects LPS-induced increase in perforin and granzyme B mRNA levels in the spleen.…”

Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spmentioning

confidence: 96%

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Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

Chen

Boyadjieva

Advis

et al. 2006

Alcoholism Clin & Exp Res

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The results demonstrate that ethanol feeding via a liquid diet for 2 weeks suppressed both basal and LPS-stimulated NK cell cytolytic functions and the levels of cytotoxicity-regulatory perforin and granzyme B mRNAs in the spleen. Ethanol feeding reduced the basal and LPS-stimulated levels of POMC mRNA in the ARC. Ethanol also impaired LPS-induced levels of IL-1beta and TNF-alpha mRNAs both in the spleen and in the ARC. In contrast, ethanol feeding did not cause any significant changes in basal and the LPS-stimulated expression of IL-6 and IL-10 mRNAs in the spleen and of IL-6 mRNA levels in the ARC. These results indicate that ethanol suppression of hypothalamic POMC levels and splenic NK cell functions is associated with a reduced expression of proinflammatory cytokines in neuroendocrine and immune cells.

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Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spsupporting

confidence: 92%

Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spsupporting

confidence: 89%

Section: Effects Of Ethanol Consumption On Basal and Lpsstimulated Spmentioning

confidence: 96%

See 1 more Smart Citation

Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

Chen

Boyadjieva

Advis

et al. 2006

Alcoholism Clin & Exp Res

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“…Ethanol significantly reduced both basal and b-endorphin-induced levels of granzyme B and IFN-c. Therefore chronic ethanol consumption suppresses bendorphin-induced NK cytolytic activity, granzyme B, and IFN-c in male Fischer-344 rats [129].…”

Section: Alcoholmentioning

confidence: 88%

“…The effects of ethanol and central administration of b-endorphin on perforin, granzyme B, and IFNc that modulate NK cell cytolytic activity were monitored to understand the mechanism involved in ethanol's suppression of NK cell activity [129]. A group of male Fischer-344 rats was fed an ethanol-containing diet (8.7% v/v), and a control group was pair-fed an isocaloric diet.…”

Section: Alcoholmentioning

confidence: 99%

Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction

Esquifino

Cano

Jiménez-Ortega

et al. 2007

Endocr

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Virtually all neuroendocrine and immunological variables investigated in animals and humans display biological periodicity. Circadian rhythmicity is revealed for every hormone in circulation as well as for circulating immune cells, lymphocyte metabolism and transformability, cytokines, receptors, and adhesion molecules. Clock genes, notably the three Period (Per1/Per2/Per3) genes and two Cryptochrome (Cry1/Cry2) genes, are present in immune and endocrine cells and are expressed in a circadian manner in human cells. This review discusses the circadian disruption of hormone release and immune-related mechanisms in several animal models in which circulating cytokines are modified including rat adjuvant arthritis, social isolation in rats and rabbits and alcoholism, the aging process and calorie restriction in rats. In every case the experimental manipulation used perturbed the temporal organization by affecting the shape and amplitude of a rhythm or by modifying the intrinsic oscillatory mechanism itself.

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The mechanisms underlying alcohol‐induced decreased splenic size: A network meta‐analysis study

Liu,

Bishir,

Hodgkinson

et al. 2023

Alcohol: Clinical and Experimental Research

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BackgroundOrgan weight change is widely accepted as a measure of toxicologic pathology. We and other groups have shown that excessive alcohol exposure leads to decreased spleen weight in rodents. This study explores the mechanisms underlying alcohol‐induced splenic injury through a network meta‐analysis.MethodsQIAGEN Ingenuity Pathway Analysis (IPA) and Mammalian Phenotype (MP) Ontology were used to identify alcohol‐related molecules associated with the small spleen phenotype. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and IPA bioinformatics tools were then used to analyze the biologic processes and enriched signaling pathways engaging these molecules. In addition, the “downstream effects analysis” algorithm was used to quantify alcohol's effects.ResultsIPA identified 623 molecules affected by alcohol and a Venn diagram revealed that 26 of these molecules overlapped with those associated with the MP Ontology of small spleen. The 26 molecules are TGFB1, CASP8, MTOR, ESR1, CXCR4, CAMK4, NFKBIA, DRD2, BCL2, FAS, PEBP1, TRAF2, ATM, IGHM, EDNRB, MDM2, GLRA1, PRF1, TLR7, IFNG, ALOX5, FOXO1, IL15, APOE, IKBKG, and RORA. Some of the 26 molecules were also associated with the MP Ontology of abnormal white pulp and red pulp morphology of the spleen, abnormal splenic cell ratio, decreased splenocyte number, abnormal spleen physiology, increased splenocyte apoptosis, and reduced splenocyte proliferation. STRING and IPA “Core Analysis” showed that these molecules were mainly involved in pathways related to cell apoptosis, proliferation, migration, and immune responses. IPA's “Molecular Activity Predictor” tool showed that concurrent effects of activation and inhibition of these molecules led to decreased spleen size by modulating apoptosis, proliferation, and migration of splenocytes.ConclusionsOur network meta‐analysis revealed that excessive alcohol exposure can damage the spleen through a variety of molecular mechanisms, thereby affecting immune function and human health. We found that alcohol‐mediated splenic atrophy is largely mediated by increased apoptosis signaling, migration of cells, and inhibition of splenocyte proliferation.

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Reduction of Perforin, Granzyme B, and Cytokine Interferon γ by Ethanol in Male Fischer 344 Rats

Abstract: These data suggest that chronic ethanol consumption may suppress NK cell cytolytic activity in male Fischer rats by decreasing the production, activity, or both of granzyme B, perforin, and IFN-gamma.

Cited by 6 publications

References 48 publications

Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

Ethanol Suppression of the Hypothalamic Proopiomelanocortin Level and the Splenic NK Cell Cytolytic Activity Is Associated With a Reduction in the Expression of Proinflammatory Cytokines but Not Anti‐inflammatory Cytokines in Neuroendocrine and Immune Cells

Neuroendocrine-immune correlates of circadian physiology: studies in experimental models of arthritis, ethanol feeding, aging, social isolation, and calorie restriction

The mechanisms underlying alcohol‐induced decreased splenic size: A network meta‐analysis study

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