Inhibition of the Kupffer Cell Inflammatory Response by Acute Ethanol: NF-κB Activation and Subsequent Cytokine Production

In pregnancy, maternal monocytes and macrophages acquire a specific phenotype that enables them to maintain immune tolerance and facilitate hormone–immune cell interactions, which are necessary for gestational progression. The aim of this study was to determine the effect of pregnancy hormone mixtures of the first and third trimesters on both resting and activated monocytes and macrophages. Pregnancy hormone levels (cortisol, estradiol, progesterone, and prolactin) were quantified at the first and third trimesters. The average of the levels obtained was used to prepare two mixtures of synthetic hormones: low and high. These mixtures were then used to stimulate THP-1 monocytes and macrophages, resting or activated with LPS. Cytokine production in the culture supernatants and surface marker expression (CD14, CD86, and CD163) were evaluated by ELISA and flow cytometry, respectively. We found that the hormones modulated the pro-inflammatory response of THP-1 cells, LPS-activated monocytes, and macrophages, inducing high levels of IL-10 and low levels of IL-8, IL-1-β, and IL-6. All hormone stimulation increased the CD163 receptor in both resting and LPS-activated monocytes and macrophages in a dose-independent manner, unlike CD14 and CD86. Pregnancy hormones promote the expression of the markers associated with the M2-like phenotype, modulating their pro-inflammatory response. This phenotype regulation by hormones could be a determinant in pregnancy.

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Roles of Specialized Pro-Resolving Lipid Mediators in Autophagy and Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms21186637 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6637 ◽

Cited By ~ 1

Author(s):

Antonio Recchiuti ◽

Elisa Isopi ◽

Mario Romano ◽

Domenico Mattoscio

Keyword(s):

Inflammatory Response ◽

Cytokine Production ◽

Lipid Mediators ◽

Tissue Homeostasis ◽

Leukocyte Infiltration ◽

Catabolic Pathway ◽

Resolution Of Inflammation ◽

Endogenous Lipid ◽

Inflammation Resolution ◽

Cellular Components

Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.

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Platelet Activation and Cytokine Production during Hypothermic Cardiopulmonary Bypass – A Possible Correlation?

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615139 ◽

1998 ◽

Vol 80 (07) ◽

pp. 58-64 ◽

Cited By ~ 22

Author(s):

P. Ferroni ◽

G. Speziale ◽

G. Ruvolo ◽

A. Giovannelli ◽

F. M. Pulcinelli ◽

...

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Inflammatory Response ◽

Platelet Activation ◽

Cytokine Production ◽

Inverse Correlation ◽

Moderate Degree ◽

Platelet Response ◽

Activated Platelets

SummaryCardiopulmonary bypass (CPB) is associated with impaired platelet function and a systemic inflammatory response. The present study was designed to evaluate whether any correlation between platelet activation and inflammatory response during CPB exists. The results obtained from 8 patients undergoing hypothermic CPB for cardiac surgery showed the occurrence of a moderate degree of platelet activation during CPB, demonstrated by an increase of platelet CD62P expression in correlation with an increase of β-thromboglobulin levels, with a concomitant decrease of in vitro platelet response. Plasma IL-1β levels significantly increased during CPB, with a peak between 1 and 4 h after CPB. Similarly, IL-6 levels were elevated 30 min from CPB starting, peaked at 4 h, and remained elevated after 24 h. A direct correlation was found between plasma IL-1β and IL-6 levels. A significant correlation between plasma IL-1β and β-thromboglobulin levels was also found. In turn, plasma β-thromboglobulin levels correlated with CD62P expression on activated platelets. An inverse correlation was found between in vitro platelet aggregation and plasma IL-1β or IL-6 levels. From the present results it may be speculated that platelet activation during CPB may contribute, through the release of IL-1β, to activation of endothelial cells and subsequent release of other cytokines with chemotactic and pro-inflammatory properties, thus playing an important role in the inflammatory response associated with CPB.

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Effects of Acute Ethanol Exposure on the Early Inflammatory Response After Excisional Injury

Alcoholism Clinical and Experimental Research ◽

10.1111/j.1530-0277.2006.00307.x ◽

2007 ◽

Vol 31 (2) ◽

pp. 317-323 ◽

Cited By ~ 38

Author(s):

Daniel J. Fitzgerald ◽

Katherine A. Radek ◽

Mitchell Chaar ◽

Douglas E. Faunce ◽

Luisa A. DiPietro ◽

...

Keyword(s):

Inflammatory Response ◽

Ethanol Exposure ◽

Acute Ethanol ◽

Early Inflammatory Response

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KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly

Cells ◽

10.3390/cells8121604 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1604 ◽

Cited By ~ 1

Author(s):

Yi Liu ◽

Wei Yin ◽

Jingwen Wang ◽

Yucong Lei ◽

Guihong Sun ◽

...

Keyword(s):

Inflammatory Response ◽

Viral Infection ◽

Zinc Finger ◽

Cytokine Production ◽

Zinc Finger Protein ◽

Nuclear Translocation ◽

Sendai Virus ◽

Positive Role ◽

Finger Protein ◽

Ikk Complex

Despite progress in understanding how virus-induced, NF-κB-dependent pro-inflammatory cytokines are regulated, there are still factors and mechanisms that remain to be explored. We aimed to uncover the relationship between KRAB-zinc finger protein ZNF268a and NF-κB-mediated cytokine production in response to viral infection. To this end, we established a ZNF268a-knockout cell line using a pair of sgRNAs that simultaneously target exon 3 in the coding sequence of the ZNF268 gene in HEK293T. HEK293T cells lacking ZNF268a showed less cytokine expression at the transcription and protein levels in response to Sendai virus/vesicular stomatitis virus (SeV/VSV) infection than wild-type cells. Consistent with HEK293T, knock-down of ZNF268a by siRNAs in THP-1 cells significantly dampened the inflammatory response. Mechanistically, ZNF268a facilitated NF-κB activation by targeting IKKα, helping to maintain the IKK signaling complex and thus enabling proper p65 phosphorylation and nuclear translocation. Taken together, our data suggest that ZNF268a plays a positive role in the regulation of virus-induced pro-inflammatory cytokine production. By interacting with IKKα, ZNF268a promotes NF-κB signal transduction upon viral infection by helping to maintain the association between IKK complex subunits.

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