Insulin Suppresses LPS-induced iNOS and COX-2 Expression and NF-&amp;kappa;B Activation in Alveolar Macrophages and

Martins, Joilson O.; Ferracini, Matheus; Ravanelli, Natalia; Landgraf, Richardt Gama; Jancar, Sônia

doi:10.1159/000149806

Cited by 49 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To our knowledge, this is the first study demonstrating an effect of thymoquinone on maturation of the immune cells. LPS exposure further stimulates the formation of IL-12, TNF-and IL-10 [31][32][33][41][42][43]. Similar to LPSinduced maturation, the LPS-induced release of IL-12, TNF-and IL-10 was blunted in the presence of thymoquinone.…”

Section: Discussionmentioning

confidence: 85%

Effect of Thymoquinone on Mouse Dendritic Cells

Xuân¹,

Shumilina²,

Qadri³

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

Thymoquinone, a component of Nigella sativa is known to confer protection against tumour growth due to stimulation of tumour cell apoptosis. Moreover, thymoquinone has remarkable anti-inflammatory potency. Surprisingly, despite its powerful influence on inflammation and its immunomodulatory effects, little is known about its effect on dendritic cells (DCs), key players in the regulation of innate and adaptive immunity. DC maturation and cytokine release is triggered by bacterial components such as lipopolysaccharides (LPS). The present study explored whether thymoquinone modifies LPS-induced DC maturation, survival and cytokine release. To this end, mouse bone marrow derived DCs were treated with LPS and different concentrations of thymoquinone and the surface expression of CD11c, CD86, MHCII, CD54 and CD40 was determined by FACS analysis, the formation of the interleukins 10 (IL-10) and 12 (IL-12p70) as well as TNF-α by ELISA, caspase activation by FITC-labelled antibodies (FACS), cell membrane scrambling by annexin V binding (FACS) and Akt and ERK1/2 phosphorylation by Western blotting. LPS increased the percentage of CD11c⁺CD86⁺, CD11c⁺MHCII⁺, CD11c⁺CD40⁺ and CD11c⁺CD54⁺ cells and stimulated the release of IL-10, IL-12p70 and TNF-α. These effects were blunted by thymoquinone in a concentration dependent manner (1-20 µM). Moreover, LPS decreased and thymoquinone increased caspase 3 and caspase 8 activation and annexin V binding. Moreover, LPS-induced phosphorylation of prosurvival kinases Akt and ERK1/2 was abrogated by thymoquinone. In conclusion, thymoquinone compromises the maturation, cytokine release and survival of DCs.

show abstract

Section: Discussionmentioning

confidence: 85%

Effect of Thymoquinone on Mouse Dendritic Cells

Xuân¹,

Shumilina²,

Qadri³

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…This is consistent with reports in mammals because insulin regulates the inflammatory response either directly or indirectly. [65][66][67][68][69][70][71][72] As in the case of the lethal LPS treatment, the lipid metabolism-related genes were affected: the low-density lipoprotein receptor (LDLR) was the most up-modulated gene at 4 dpf. Because LPS can be bound by triglyceride-rich lipoproteins (TRL) that may be internalized through the LDLR pathway, the internalization of lipoprotein bound endotoxin (TRL-LPS) could attenuate the systemic inflammatory response.…”

Section: Dios Et Almentioning

confidence: 99%

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

Dios

Balseiro²,

Costa³

et al. 2014

Zebrafish

View full text Add to dashboard Cite

Septic shock is the most common cause of death in intensive care units due to an aggressive inflammatory response that leads to multiple organ failure. However, a lipopolysaccharide (LPS) tolerance phenomenon (a nonreaction to LPS), is also often described. Neither the inflammatory response nor the tolerance is completely understood. In this work, both of these responses were analyzed using microarrays in zebrafish. Fish that were 4 or 6 days postfertilization (dpf) and received a lethal dose (LD) of LPS exhibited 100% mortality in a few days. Their transcriptome profile, even at 4 dpf, resembled the profile in humans with severe sepsis. Moreover, we selected 4-dpf fish to set up a tolerance protocol: fish treated with a nonlethal concentration of Escherichia coli LPS exhibited complete protection against the LD of LPS. Most of the main inflammatory molecules described in mammals were represented in the zebrafish microarray experiments. Additionally and focusing on this tolerance response, the use of cyclodextrins may mobilize cholesterol reservoirs to decrease mortality after a LD dose of LPS. Therefore, it is possible that the use of the whole animal could provide some clues to enhance the understanding of the inflammatory/tolerance response and to guide drug discovery.

show abstract

“…The data presented herein show that insulin restored the phosphorylation of Ser-473 Akt which was reduced in diabetic rats. This suggests that insulin could act directly on p21 ras , which favours the hypothesis that the immune hyporesponsiveness in diabetic patients is due to the modulation of cellular signal transcription factors [17,22] rather than to changes in metabolism and blood glucose levels [1][2][3][4][5][6][7][8].…”

Section: Discussionmentioning

confidence: 88%

Early Phase of Allergic Airway Inflammation in Diabetic Rats: Role of Insulin on the Signaling Pathways and Mediators

Martins

Wittlin

Anger

et al. 2010

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background: Allergic lung inflammation is impaired in diabetic rats and is restored by insulin treatment. In the present study we investigated the effect of insulin on the signaling pathways triggered by allergic inflammation in the lung and the release of selected mediators. Methods: Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and matching controls were sensitized by s.c. injections of ovalbumin (OA) in aluminium hydroxide, 14 days before OA (1 mg/0.4 ml) or saline intratracheal challenge. A group of diabetic rats were treated with neutral protamine Hagedorn insulin (NPH, 4 IU, s.c.), 2 h before the OA challenge. Six hours after the challenge, bronchoalveolar lavage (BAL) was performed for mediator release and lung tissue was homogenized for Western blotting analysis of signaling pathways. Results: Relative to non-diabetic rats, the diabetic rats exhibited a significant reduction in OA-induced phosphorylation of the extracellular signal-regulated kinase (ERK, 59%), p38 (53%), protein kinase B (Akt, 46%), protein kinase C (PKC)- α (63%) and PKC-δ (38%) in lung homogenates following the antigen challenge. Activation of the NF-ĸB p65 subunit and phosphorylation of IĸBα were almost suppressed in diabetic rats. Reduced expression of inducible nitric oxide synthase (iNOS, 32%) and cyclooxygenase-2 (COX-2, 46%) in the lung homogenates was also observed. The BAL concentration of prostaglandin (PG)-E₂, nitric oxide (NO) and interleukin (IL)-6 was reduced in diabetic rats (74%, 44% and 65%, respectively), whereas the cytokine-induced neutrophil chemoattractant (CINC)-2 concentration was not different from the control animals. Treatment of diabetic rats with insulin completely or partially restored all of these parameters. This protocol of insulin treatment only partially reduced the blood glucose levels. Conclusion: The data presented show that insulin regulates MAPK, PI3K, PKC and NF-ĸB pathways, the expression of the inducible enzymes iNOS and COX-2, and the levels of NO, PGE₂ and IL-6 in the early phase of allergic lung inflammation in diabetic rats. It is suggested that insulin is required for optimal transduction of the intracellular signals that follow allergic stimulation.

show abstract

Insulin Suppresses LPS-induced iNOS and COX-2 Expression and NF-κB Activation in Alveolar Macrophages and

Cited by 49 publications

References 28 publications

Effect of Thymoquinone on Mouse Dendritic Cells

Effect of Thymoquinone on Mouse Dendritic Cells

The Involvement of Cholesterol in Sepsis and Tolerance to Lipopolysaccharide Highlighted by the Transcriptome Analysis of Zebrafish (Danio rerio)

Early Phase of Allergic Airway Inflammation in Diabetic Rats: Role of Insulin on the Signaling Pathways and Mediators

Contact Info

Product

Resources

About