Role of STAT6 and mast cells in IL-4-and IL-13-induced alterations in murine intestinal epithelial cell function
Role of STAT6 and mast cells in IL-4-and IL-13-induced alterations in murine intestinal epithelial cell function
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DOI：
10.4049/jimmunol.169.8.4417
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发表时间：
2002-10-15
影响因子：
4.4
通讯作者：
Shea-Donohue, T
中科院分区：
文献类型：
--
作者：
Madden, KB;Whitman, L;Shea-Donohue, T
胃肠道线虫感染通常引起2型细胞因子应答，其特征在于产生IL-4、IL-5、IL-9和IL-13。在这些细胞因子中，IL-4和IL-13表现出功能重叠，这可以通过共享共同的受体或受体组分（IL-4 R α）来解释。1型或2型IL-4 R与IL-4的结合，或2型IL-4 R与IL-13的结合，启动IL-4 α链和转录因子STAT 6的Jak依赖性酪氨酸磷酸化。在本研究中，我们研究了：1）IL-13是否对肠上皮细胞具有与IL-4相似的作用，以及2）IL-4和IL-13的作用是否依赖于STAT 6信号传导和/或肥大细胞。BALB/c、STAT 6（-/-）和肥大细胞缺陷型W/W-v小鼠或其+/+同窝仔用重组小鼠IL-4（IL-4C）或IL-13的长效制剂处理7天。将空肠段固定在Ussing室中，以测量粘膜通透性;对PGE（2）、组胺、5-羟色胺或乙酰胆碱的反应性氯化物分泌;以及Na+-连接的葡萄糖吸收。IL-4C和IL-13增加粘膜通透性，减少葡萄糖吸收，并减少氯化物分泌，以响应5-羟色胺。这些作用依赖于STAT 6信号传导。对PGE（2）和组胺的反应依赖于肥大细胞和STAT 6，IL-4C可增强这些反应，但IL-13则无此作用。IL-4和IL-13对肠上皮细胞功能的影响可能在宿主保护胃肠道线虫中起关键作用。
Gastrointestinal nematode infections generally invoke a type 2 cytokine response, characterized by the production of IL-4, IL-5, IL-9, and IL-13. Among these cytokines, IL-4 and IL-13 exhibit a functional overlap that can be explained by the sharing of a common receptor or receptor component (IL-4Ralpha). Binding of IL-4 by either the type 1 or 2 IL-4R, or of IL-13 by the type 2 IL-4R, initiates Jak-dependent tyrosine phosphorylation of the IL-4Ralpha-chain and the transcription factor, STAT6. In the present study, we investigated: 1) whether IL-13 has effects on intestinal epithelial cells similar to those observed with IL-4, and 2) whether the effects of IL-4 and IL-13 depend on STAT6 signaling and/or mast cells. BALB/c, STAT6(-/-), and mast cell-deficient W/W-v mice or their +/+ littermates were treated with a long-lasting formulation of recombinant mouse IL-4 (IL-4C) or with IL-13 for seven days. Segments of jejunum were mounted in Ussing chambers to measure mucosal permeability; chloride secretion in response to PGE(2), histamine, 5-hydroxytryptamine, or acetylcholine; and Na+-linked glucose absorption. IL-4C and IL-13 increased mucosal permeability, decreased glucose absorption, and decreased chloride secretion in response to 5-hydroxytryptamine. These effects were dependent on STAT6 signaling. Responses to PGE(2) and histamine, which were dependent on mast cells and STAT6, were enhanced by IL-4C, but not by IL-13. The effects of IL-4 and IL-13 on intestinal epithelial cell function may play a critical role in host protection against gastrointestinal nematodes.