Yamauchi Yoko, Fujikura Terumichi, Shimosawa Tatsuo
Department of Otorhinolaryngology, Nippon Medical School, Kanagawa, Japan.
Allergol Int. 2007 Jun;56(2):171-7. doi: 10.2332/allergolint.O-06-446. Epub 2007 May 1.
CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy.
HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.
The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups.
This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.
CC趋化因子已被证明在诱导炎症细胞选择性募集到局部过敏性炎症部位中发挥重要作用。CC趋化因子也被称为组胺释放因子。我们之前表明组胺可增强鼻黏膜中CC趋化因子的转录，这会导致组胺释放的进一步诱导。这种循环级联反应可能会导致过敏性炎症的持续。本研究的目的是利用人鼻上皮细胞（HNECs）阐明组胺与CC趋化因子产生之间的关系，并研究H1受体（H1R）拮抗剂在治疗鼻过敏新疗法中的潜力。
从被诊断为鼻过敏的患者鼻甲中分离出HNECs。将HNEC单层细胞在有或无组胺（10⁻³至10⁻⁵mol/L）的条件下培养48小时。此外，在与组胺孵育前半小时，将H1R拮抗剂卡巴斯汀或奥洛他定添加到上清液中（10⁻³至10⁻⁷mol/L）。通过酶联免疫吸附测定法测量培养基中调节激活正常T细胞表达和分泌因子（RANTES）及单核细胞趋化蛋白-1（MCP-1）的表达。
与对照组相比，组胺显著上调了RANTES和MCP-1的释放。卡巴斯汀和奥洛他定都将两组中CC趋化因子的产生释放抑制到了对照水平。
本研究表明组胺与CC趋化因子之间的相互作用可能会延长人鼻黏膜中的过敏性炎症。我们还证明了H1R拮抗剂通过抑制这种组胺-CC趋化因子相互作用在治疗鼻过敏新疗法中的潜在用途。
