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Δ(9)-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor in human monocytes and monocyte-derived microvesicles.

Williams JC, Klein TW, Goldberger BA, Sleasman JW, Mackman N, Goodenow MM - J Inflamm (Lond) (2015)

Bottom Line: Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC.Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment.In contrast, TNF and IL-8 levels were enhanced by 20-50 %.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Gainesville, FL 32610-3663 USA.

ABSTRACT

Background: Immunomodulatory effects in humans of Δ(9-)Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated.

Findings: Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20-50 %.

Conclusions: THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus

Effect of THC on pro-inflammatory cytokine stimulated by LPS. mRNA or cell supernatants (protein) from monocytes from at least 4 donors were treated with vehicle or 30 μM THC for 30 min prior to the addition of 100 ng/mL LPS for 24 h. Real-time quantitative PCR or ELISAs for (a) IL-6, b TNFα, and c IL-8 were performed and graphed relative to vehicle control at each time point (dotted line at 1). Left panels show mean and standard error of donors
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Fig4: Effect of THC on pro-inflammatory cytokine stimulated by LPS. mRNA or cell supernatants (protein) from monocytes from at least 4 donors were treated with vehicle or 30 μM THC for 30 min prior to the addition of 100 ng/mL LPS for 24 h. Real-time quantitative PCR or ELISAs for (a) IL-6, b TNFα, and c IL-8 were performed and graphed relative to vehicle control at each time point (dotted line at 1). Left panels show mean and standard error of donors

Mentions: To explore the mechanism by which THC enhanced LPS-stimulated TF expression and activity, selected signal transduction events were investigated. Although TF expression is dependent on ERK1/2 and NF-κB signaling [2, 3], phosphorylation of ERK1/2 and p65 or degradation of IκBα were unchanged (Fig. 3a-d). Since signal transduction is unaltered, it is unlikely that THC ubiquitously promotes inflammation, rather THC imparts an effect that is TF specific. Moreover, TNFα or IL-8 mRNA and secreted protein increased modestly with THC treatment, while IL-6 was unchanged (Fig. 4). In addition, while THC treatment results in modest increases in IL-8 and TNFα, THC mediated elevations in TF are of a greater magnitude. However, as TNFα stimulates TF expression [22], small elevations in TNFα expression may act synergistically with other mechanisms to further enhance THC mediated elevations in TF expression and activity.Fig. 3


Δ(9)-Tetrahydrocannabinol (THC) enhances lipopolysaccharide-stimulated tissue factor in human monocytes and monocyte-derived microvesicles.

Williams JC, Klein TW, Goldberger BA, Sleasman JW, Mackman N, Goodenow MM - J Inflamm (Lond) (2015)

Effect of THC on pro-inflammatory cytokine stimulated by LPS. mRNA or cell supernatants (protein) from monocytes from at least 4 donors were treated with vehicle or 30 μM THC for 30 min prior to the addition of 100 ng/mL LPS for 24 h. Real-time quantitative PCR or ELISAs for (a) IL-6, b TNFα, and c IL-8 were performed and graphed relative to vehicle control at each time point (dotted line at 1). Left panels show mean and standard error of donors
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4469459&req=5

Fig4: Effect of THC on pro-inflammatory cytokine stimulated by LPS. mRNA or cell supernatants (protein) from monocytes from at least 4 donors were treated with vehicle or 30 μM THC for 30 min prior to the addition of 100 ng/mL LPS for 24 h. Real-time quantitative PCR or ELISAs for (a) IL-6, b TNFα, and c IL-8 were performed and graphed relative to vehicle control at each time point (dotted line at 1). Left panels show mean and standard error of donors
Mentions: To explore the mechanism by which THC enhanced LPS-stimulated TF expression and activity, selected signal transduction events were investigated. Although TF expression is dependent on ERK1/2 and NF-κB signaling [2, 3], phosphorylation of ERK1/2 and p65 or degradation of IκBα were unchanged (Fig. 3a-d). Since signal transduction is unaltered, it is unlikely that THC ubiquitously promotes inflammation, rather THC imparts an effect that is TF specific. Moreover, TNFα or IL-8 mRNA and secreted protein increased modestly with THC treatment, while IL-6 was unchanged (Fig. 4). In addition, while THC treatment results in modest increases in IL-8 and TNFα, THC mediated elevations in TF are of a greater magnitude. However, as TNFα stimulates TF expression [22], small elevations in TNFα expression may act synergistically with other mechanisms to further enhance THC mediated elevations in TF expression and activity.Fig. 3

Bottom Line: Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC.Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment.In contrast, TNF and IL-8 levels were enhanced by 20-50 %.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Gainesville, FL 32610-3663 USA.

ABSTRACT

Background: Immunomodulatory effects in humans of Δ(9-)Tetrahydrocannabinol (THC), the psychoactive component of marijuana are controversial. Tissue factor (TF), the activator of the extrinsic coagulation cascade, is increased on circulating activated monocytes and is expressed on microvesicles released from activated monocytes during inflammatory conditions, which perpetuate coagulopathies in a number of diseases. In view of the increased medicinal use of marijuana, effects of THC on human monocytes and monocyte-derived microvesicles activated by lipopolysaccharide (LPS) were investigated.

Findings: Peak levels of TF procoagulant activity developed in monocytes or microvesicles 6 h following LPS treatment and were unaltered by THC. After 24 h of LPS stimulation, TF activity declined in control-treated or untreated cells and microvesicles, but persisted with THC treatment. Peak TF protein occurred within 6 h of LPS treatment independent of THC; by 24 h, TF protein declined to almost undetectable levels without THC, but was about 4-fold greater with THC. Steady-state TF mRNA levels were similar up to 2 h in the presence of LPS with or without THC, while 10-fold greater TF mRNA levels persisted over 3-24 h with THC treatment. Activation of MAPK or NF-κB pathways was unaltered by THC treatment and inflammatory cytokine IL-6 levels were unchanged. In contrast, TNF and IL-8 levels were enhanced by 20-50 %.

Conclusions: THC enhances TF expression in activated monocytes resulting in elevated procoagulant activity. Marijuana use could potentiate coagulopathies in individuals with chronic immune activation such as HIV-1 infection or inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus