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

Clin Exp Dermatol. 2005 Mar;30(2):165-70. doi: 10.1111/j.1365-2230.2005.01721.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Benzimidazoles / pharmacology*
  • Cells, Cultured
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Cytokines / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Histamine H1 Antagonists / pharmacology*
  • Loratadine / pharmacology
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mice
  • RNA, Messenger / genetics
  • Receptors, IgE / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inducing Agents
  • Anti-Inflammatory Agents
  • Benzimidazoles
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Cxcl1 protein, mouse
  • Cytokines
  • Histamine H1 Antagonists
  • RNA, Messenger
  • Receptors, IgE
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • keratinocyte-derived chemokines
  • mizolastine
  • Loratadine
  • Dexamethasone