The effect of mizolastine on expression of vascular endothelial cell growth factor, tumour necrosis factor-alpha and keratinocyte-derived chemokine in murine mast cells, compared with dexamethasone and loratadine.
It has been shown that many antihistamines may have anti-inflammatory activity in addition to being H1 antagonists. Mizolastine (MIZ), a novel antihistamine, might also have anti-angiogenesis properties. In this study, we investigated the influence of MIZ on proangiogenesis factors, vascular endothelial cell growth factor (VEGF), tumour necrosis factor (TNF)-alpha and keratinocyte-derived chemokine (KC) in murine mast cells by using ELISA and RT-PCR, as compared with dexamethasone (DEX) and loratadine (LOR). Our results show that MIZ is effective in the inhibition of KC, VEGF and TNF-alpha release induced by an IgE-dependent mechanism, in a time- and dose-dependent manner. The differences between the inhibitory effects of the three drugs on these proangiogenic factors were rather subtle. Semiquantitative analysis using RT-PCR showed that the three drugs significantly reduced VEGF165, VEGF120, TNF-alpha and KC mRNA expression. Statistical results revealed that the effect of DEX on VEGF165 mRNA was different from that of MIZ or LOR (P < 0.01) and the differences between the three drugs on VEGF120, TNF-alpha and KC mRNA were not statistically significant (P > 0.05). These findings raise the possibility that MIZ can mediate anti-angiogenesis activity and that the effect may depend not only on the inhibition on the levels of cytokine proteins but also at the mRNA level.
Xia
Q
Q
Institute of Dermatology & Department of Dermatology at no. 1 Hospital, Anhui Medical University, Hefei, Anhui, PR China.
Yang
S
S
Zhang
S Q
SQ
Chen
B
B
Wang
D B
DB
Zhu
Q X
QX
Wang
Y
Y
Yan
K L
KL
He
P P
PP
Zhang
X J
XJ
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D017336:Loratadine / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D017455:Receptors, IgE / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D006634:Histamine H1 Antagonists; D012333:RNA, Messenger; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C074302:keratinocyte-derived chemokines; C076170:mizolastine; D017336:Loratadine; D003907:Dexamethasone