Bossios A, Gourgiotis D, Skevaki C L, Saxoni-Papageorgiou P, Lötvall J, Psarras S, Karpathios T, Constandopoulos A G, Johnston S L, Papadopoulos N G
Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.
Clin Exp Allergy. 2008 Oct;38(10):1615-26. doi: 10.1111/j.1365-2222.2008.03058.x. Epub 2008 Jul 18.
Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved.
To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro.
BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured.
RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8.
HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.
人鼻病毒（HRVs）和屋尘螨（HDMs）是能够诱发哮喘气道炎症的最常见环境因素。尽管流行病学研究表明它们在诱发哮喘急性发作方面也存在协同作用，但尚无实验证据支持这一点，也没有关于可能涉及的机制的任何信息。
研究它们在体外诱导气道上皮炎症反应中的相互作用。
将BEAS-2B细胞以不同顺序暴露于活化的HDM 主要变应原I（Der p I）、HRVs（HRV1b或HRV16）或两者。评估白细胞介素-8/CXCL8释放、细胞间黏附分子（ICAM）-1表面表达和核因子κB（NF-κB）易位。作为补充，检测了暴露于Der p I和鼻病毒的原代人支气管上皮细胞（HBECs）以及白细胞介素-8、白细胞介素-6、干扰素-γ诱导蛋白（IP）-10/CXCL10、干扰素-λ1/白细胞介素-29、活化正常T淋巴细胞表达和分泌的调节趋化因子（RANTES）/CCL5的释放。
鼻病毒和Der p I上调BEAS-2B细胞中白细胞介素-8释放、ICAM-1表达和NF-κB易位。同时暴露于这两种因素，以及细胞最初暴露于鼻病毒然后暴露于Der p I时，均以协同方式进一步诱导白细胞介素-8。当细胞最初暴露于Der p I然后暴露于鼻病毒时未观察到协同作用。这是ICAM-1诱导的模式，尽管该现象不是协同的。同时暴露诱导早期协同的NF-κB易位诱导，随时间推移有所不同，部分解释了上述观察结果。在HBECs中，鼻病毒和Der p I均诱导白细胞介素-8、白细胞介素-6、白细胞介素-29和IP-10，而RANTES仅由鼻病毒诱导。仅在白细胞介素-8中观察到协同诱导。
当鼻病毒感染先于或与Der p I暴露同时发生时，鼻病毒和具有酶活性的Der p I可在诱导支气管上皮白细胞介素-8释放中协同作用。这种协同作用可能是病毒诱发哮喘急性发作的重要机制。
