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Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

Je IG, Kim DS, Kim SW, Lee S, Lee HS, Park EK, Khang D, Kim SH - PLoS ONE (2015)

Bottom Line: Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines.Our results showed that PI3K could be a molecular target for tyrosol in mast cells.Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.

ABSTRACT
Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

No MeSH data available.


Related in: MedlinePlus

Effects of tyrosol on the activation of signaling proteins.RBL-2H3 cells (2 × 106/well) were sensitized with anti-DNP IgE (50 ng/ml). After incubating overnight, the cells were pretreated with or without tyrosol for 1 h and then challenged with DNP-HSA (100 ng/ml). Extraction of protein was performed as described in the Materials and methods section. Activation of signaling proteins was assayed by Western blot (p-: phosphorylated). The band of total form was used as a loading control. PP2, a Src family inhibitor, was used as a positive control. The band is a representative of three independent experiments.
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pone.0129829.g006: Effects of tyrosol on the activation of signaling proteins.RBL-2H3 cells (2 × 106/well) were sensitized with anti-DNP IgE (50 ng/ml). After incubating overnight, the cells were pretreated with or without tyrosol for 1 h and then challenged with DNP-HSA (100 ng/ml). Extraction of protein was performed as described in the Materials and methods section. Activation of signaling proteins was assayed by Western blot (p-: phosphorylated). The band of total form was used as a loading control. PP2, a Src family inhibitor, was used as a positive control. The band is a representative of three independent experiments.

Mentions: The intracellular signaling pathways in mast cells have been determined in detail [4]. To assure the phosphorylation of signaling proteins such as Lyn, Syk, PI3K, and Akt, Western blots were performed. Tyrosol did not affect the activation of Lyn and Syk, on the contrary, it reduced the phosphorylation of PI3K and Akt (Fig 6).


Tyrosol Suppresses Allergic Inflammation by Inhibiting the Activation of Phosphoinositide 3-Kinase in Mast Cells.

Je IG, Kim DS, Kim SW, Lee S, Lee HS, Park EK, Khang D, Kim SH - PLoS ONE (2015)

Effects of tyrosol on the activation of signaling proteins.RBL-2H3 cells (2 × 106/well) were sensitized with anti-DNP IgE (50 ng/ml). After incubating overnight, the cells were pretreated with or without tyrosol for 1 h and then challenged with DNP-HSA (100 ng/ml). Extraction of protein was performed as described in the Materials and methods section. Activation of signaling proteins was assayed by Western blot (p-: phosphorylated). The band of total form was used as a loading control. PP2, a Src family inhibitor, was used as a positive control. The band is a representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465982&req=5

pone.0129829.g006: Effects of tyrosol on the activation of signaling proteins.RBL-2H3 cells (2 × 106/well) were sensitized with anti-DNP IgE (50 ng/ml). After incubating overnight, the cells were pretreated with or without tyrosol for 1 h and then challenged with DNP-HSA (100 ng/ml). Extraction of protein was performed as described in the Materials and methods section. Activation of signaling proteins was assayed by Western blot (p-: phosphorylated). The band of total form was used as a loading control. PP2, a Src family inhibitor, was used as a positive control. The band is a representative of three independent experiments.
Mentions: The intracellular signaling pathways in mast cells have been determined in detail [4]. To assure the phosphorylation of signaling proteins such as Lyn, Syk, PI3K, and Akt, Western blots were performed. Tyrosol did not affect the activation of Lyn and Syk, on the contrary, it reduced the phosphorylation of PI3K and Akt (Fig 6).

Bottom Line: Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines.Our results showed that PI3K could be a molecular target for tyrosol in mast cells.Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.

ABSTRACT
Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.

No MeSH data available.


Related in: MedlinePlus