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Dexmedetomidine Modulates Histamine-induced Ca(2+) Signaling and Pro-inflammatory Cytokine Expression.

Yang D, Hong JH - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+).Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine.Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon 406-799, Korea.

ABSTRACT
Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing α2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca(2+) release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca(2+) signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+). When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca(2+)]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

No MeSH data available.


Related in: MedlinePlus

Effects of dexmedetomidine on histamine-induced IL-6 and IL-8 mRNA expression. (A) After pre-treatment with 100 ng/mL dexmedetomidine (Dex) for 30 min, HeLa cells were stimulated with PBS and 100 nM histamine (His) for 90 min and then total RNA was extracted and amplified with primers specific for IL-6, IL-8, and GAPDH. Data are from one of experimental replicates. IL-6 (B) and IL-8 mRNA (C) expressions were quantified after normalizing to GAPDH levels as a loading control (n=6 and n=3, respectively). Results are the means±SEMs of independent experiments. M: DNA ladder (bp), PBS: phosphate buffered saline. *p<0.01 was considered statistically significant.
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Figure 4: Effects of dexmedetomidine on histamine-induced IL-6 and IL-8 mRNA expression. (A) After pre-treatment with 100 ng/mL dexmedetomidine (Dex) for 30 min, HeLa cells were stimulated with PBS and 100 nM histamine (His) for 90 min and then total RNA was extracted and amplified with primers specific for IL-6, IL-8, and GAPDH. Data are from one of experimental replicates. IL-6 (B) and IL-8 mRNA (C) expressions were quantified after normalizing to GAPDH levels as a loading control (n=6 and n=3, respectively). Results are the means±SEMs of independent experiments. M: DNA ladder (bp), PBS: phosphate buffered saline. *p<0.01 was considered statistically significant.

Mentions: Changes in [Ca2+]i are intimately involved in various stress responses and the inflammatory responses elicit by pro-inflammatory cytokines and chemokines [212223]. Even though Ca2+ signaling itself do not dictate cytokine induction, it is quite clear that Ca2+ is an important control element for the induction of cytokines and facilitates this process [24]. To assess the effect of dexmedetomidine on histamine-mediated IL-6 and IL-8 production, cells were pretreated with 100 ng/mL dexmedetomidine for 30 min and then treated with 100 nM histamine for 90 min. Histamine increased IL-6 mRNA level (Fig. 4), whereas pretreatement with dexmedetomidine suppressed histamine-mediated IL-6 mRNA expression to 55.8% compared to histamine-treated cells (Fig. 4B and 4C). Histamine stimulation did not alter IL-8 mRNA expression within 2 hrs. These findings suggested that dexmedetomidine potently inhibited histamine signaling by suppressing histamine-induced expression of the pro-inflammatory cytokine IL-6.


Dexmedetomidine Modulates Histamine-induced Ca(2+) Signaling and Pro-inflammatory Cytokine Expression.

Yang D, Hong JH - Korean J. Physiol. Pharmacol. (2015)

Effects of dexmedetomidine on histamine-induced IL-6 and IL-8 mRNA expression. (A) After pre-treatment with 100 ng/mL dexmedetomidine (Dex) for 30 min, HeLa cells were stimulated with PBS and 100 nM histamine (His) for 90 min and then total RNA was extracted and amplified with primers specific for IL-6, IL-8, and GAPDH. Data are from one of experimental replicates. IL-6 (B) and IL-8 mRNA (C) expressions were quantified after normalizing to GAPDH levels as a loading control (n=6 and n=3, respectively). Results are the means±SEMs of independent experiments. M: DNA ladder (bp), PBS: phosphate buffered saline. *p<0.01 was considered statistically significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 4: Effects of dexmedetomidine on histamine-induced IL-6 and IL-8 mRNA expression. (A) After pre-treatment with 100 ng/mL dexmedetomidine (Dex) for 30 min, HeLa cells were stimulated with PBS and 100 nM histamine (His) for 90 min and then total RNA was extracted and amplified with primers specific for IL-6, IL-8, and GAPDH. Data are from one of experimental replicates. IL-6 (B) and IL-8 mRNA (C) expressions were quantified after normalizing to GAPDH levels as a loading control (n=6 and n=3, respectively). Results are the means±SEMs of independent experiments. M: DNA ladder (bp), PBS: phosphate buffered saline. *p<0.01 was considered statistically significant.
Mentions: Changes in [Ca2+]i are intimately involved in various stress responses and the inflammatory responses elicit by pro-inflammatory cytokines and chemokines [212223]. Even though Ca2+ signaling itself do not dictate cytokine induction, it is quite clear that Ca2+ is an important control element for the induction of cytokines and facilitates this process [24]. To assess the effect of dexmedetomidine on histamine-mediated IL-6 and IL-8 production, cells were pretreated with 100 ng/mL dexmedetomidine for 30 min and then treated with 100 nM histamine for 90 min. Histamine increased IL-6 mRNA level (Fig. 4), whereas pretreatement with dexmedetomidine suppressed histamine-mediated IL-6 mRNA expression to 55.8% compared to histamine-treated cells (Fig. 4B and 4C). Histamine stimulation did not alter IL-8 mRNA expression within 2 hrs. These findings suggested that dexmedetomidine potently inhibited histamine signaling by suppressing histamine-induced expression of the pro-inflammatory cytokine IL-6.

Bottom Line: Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+).Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine.Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon 406-799, Korea.

ABSTRACT
Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing α2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca(2+) release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca(2+) signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+). When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca(2+)]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

No MeSH data available.


Related in: MedlinePlus