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Novel functional aspect of antihistamines: the impact of bepotastine besilate on substance p-induced events.

Kitaba S, Murota H, Yahata Y, Azukizawa H, Katayama I - J Allergy (Cairo) (2009)

Bottom Line: Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases.Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs).Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs.

View Article: PubMed Central - PubMed

Affiliation: Course of Integrated Medicine, Department of Dermatology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-Shi, Osaka 565-0871, Japan.

ABSTRACT
Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases. Although antihistamines are frequently used for pruritic skin diseases, little is known concerning the effect on an SP-induced event such as mast cell degranulation and the upregulation of adhesion molecules or the nitric oxide (NO) synthesis in endothelial cells. Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs). Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs. Bepotastine besilate significantly inhibited expression of adhesion molecules in HMVESs, while it failed to suppress SP-induced upregulation of the adhesion molecules in HMVECs. Therefore, bepotastine besilate is assumed to act favorably on SP-induced basophil degranulation and NO synthesis in HMVECs.

No MeSH data available.


Related in: MedlinePlus

Cell surface expression level of ICAM1 and P-selectin on HMVEC with various treatments. (a) Representative data of an FACS analysis for ICAM1. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (b) The graph shows the mean fluorescence intensity of immunolabeled ICAM1. Mean FL: mean fluorescence. Error bar: SD. N = 3. (c) Representative data of an FACS analysis for P-selectin. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (d) The graph shows the mean fluorescence intensity of immunolabeled P-selectin. Mean FL: mean fluorescence. Error bar: SD. N = 3.
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fig3: Cell surface expression level of ICAM1 and P-selectin on HMVEC with various treatments. (a) Representative data of an FACS analysis for ICAM1. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (b) The graph shows the mean fluorescence intensity of immunolabeled ICAM1. Mean FL: mean fluorescence. Error bar: SD. N = 3. (c) Representative data of an FACS analysis for P-selectin. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (d) The graph shows the mean fluorescence intensity of immunolabeled P-selectin. Mean FL: mean fluorescence. Error bar: SD. N = 3.

Mentions: Next, to verify the response of the HMVECs against SP, the HMVECs were treated with 1 × 10−6 and 1 × 10−4 M of SP or vehicle for 24 hours, and the medium concentration of sICAM1 and sVCAM1 were measured (Figure 2(a)). Unexpectedly, no significant differences were observed between the SP-treated and untreated groups. To verify the localization and expression level of ICAM1 and P-selectin in the HMVECs, immunochemical staining was performed (Figure 2(b)). However, there are no significant changes between the SP-treated and untreated groups. Interestingly, when the HMVECs were treated with bepotastine besilate alone, the cell surface expression level of ICAM-1 or P-selectin had a tendency to decrease (Figure 2(b)). To verify the above results, an FACS analysis for ICAM-1 and P-selectin was performed (Figure 3). The cell surface expression level of ICAM-1 and P-selectin slightly, but significantly, increased on the SP-treated HMVECs. Although, both bepotastine besilate and pyliramine did not affect the SP-induced upregulation of ICAM-1 and P-selectin, a significant decrease of the expression level of these adhesion molecules on the HMVECs treated with bepotastine besilate alone was reproduced by this assay.


Novel functional aspect of antihistamines: the impact of bepotastine besilate on substance p-induced events.

Kitaba S, Murota H, Yahata Y, Azukizawa H, Katayama I - J Allergy (Cairo) (2009)

Cell surface expression level of ICAM1 and P-selectin on HMVEC with various treatments. (a) Representative data of an FACS analysis for ICAM1. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (b) The graph shows the mean fluorescence intensity of immunolabeled ICAM1. Mean FL: mean fluorescence. Error bar: SD. N = 3. (c) Representative data of an FACS analysis for P-selectin. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (d) The graph shows the mean fluorescence intensity of immunolabeled P-selectin. Mean FL: mean fluorescence. Error bar: SD. N = 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958303&req=5

fig3: Cell surface expression level of ICAM1 and P-selectin on HMVEC with various treatments. (a) Representative data of an FACS analysis for ICAM1. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (b) The graph shows the mean fluorescence intensity of immunolabeled ICAM1. Mean FL: mean fluorescence. Error bar: SD. N = 3. (c) Representative data of an FACS analysis for P-selectin. The X axis indicates the fluorescence intensity. The Y axis represents the cell count number. The heading includes the data of mean fluorescence. (d) The graph shows the mean fluorescence intensity of immunolabeled P-selectin. Mean FL: mean fluorescence. Error bar: SD. N = 3.
Mentions: Next, to verify the response of the HMVECs against SP, the HMVECs were treated with 1 × 10−6 and 1 × 10−4 M of SP or vehicle for 24 hours, and the medium concentration of sICAM1 and sVCAM1 were measured (Figure 2(a)). Unexpectedly, no significant differences were observed between the SP-treated and untreated groups. To verify the localization and expression level of ICAM1 and P-selectin in the HMVECs, immunochemical staining was performed (Figure 2(b)). However, there are no significant changes between the SP-treated and untreated groups. Interestingly, when the HMVECs were treated with bepotastine besilate alone, the cell surface expression level of ICAM-1 or P-selectin had a tendency to decrease (Figure 2(b)). To verify the above results, an FACS analysis for ICAM-1 and P-selectin was performed (Figure 3). The cell surface expression level of ICAM-1 and P-selectin slightly, but significantly, increased on the SP-treated HMVECs. Although, both bepotastine besilate and pyliramine did not affect the SP-induced upregulation of ICAM-1 and P-selectin, a significant decrease of the expression level of these adhesion molecules on the HMVECs treated with bepotastine besilate alone was reproduced by this assay.

Bottom Line: Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases.Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs).Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs.

View Article: PubMed Central - PubMed

Affiliation: Course of Integrated Medicine, Department of Dermatology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita-Shi, Osaka 565-0871, Japan.

ABSTRACT
Besides histamine, substance P (SP) has been demonstrated to play a crucial role in pruritic skin diseases. Although antihistamines are frequently used for pruritic skin diseases, little is known concerning the effect on an SP-induced event such as mast cell degranulation and the upregulation of adhesion molecules or the nitric oxide (NO) synthesis in endothelial cells. Our aim was to study the effect of bepotastine besilate on SP-induced degranulation of rat basophillic leukemia (RBL-2H3) cells and expression of adhesion molecules and NO synthesis in human dermal microvascular endothelial cells (HMVECs). Bepotastine besilate significantly inhibited SP-induced degranulation of RBL-2H3 cells and NO synthesis in HMVECs. Bepotastine besilate significantly inhibited expression of adhesion molecules in HMVESs, while it failed to suppress SP-induced upregulation of the adhesion molecules in HMVECs. Therefore, bepotastine besilate is assumed to act favorably on SP-induced basophil degranulation and NO synthesis in HMVECs.

No MeSH data available.


Related in: MedlinePlus