Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells.
Regulation of IL-13 production by histamine in cloned murine T helper type 2 cells.
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组胺对克隆鼠 2 型辅助 T 细胞中 IL-13 产生的调节。
DOI：
10.1016/s1567-5769(01)00117-5
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Khan,MM
中科院分区：
文献类型：
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作者：
Elliott,KA;Osna,NA;Scofield,MA;Khan,MM
组胺通过将细胞因子的产生从Th 1模式转变为Th 2模式来影响辅助性T细胞1型（Th 1）和辅助性T细胞2型（Th 2）细胞因子的平衡。白细胞介素-13（IL-13）是一种重要的自体免疫介质，与过敏性疾病的发生发展有关。本研究旨在探讨组胺对Th 2细胞IL-13的调节机制。用组胺（10−8-10− 4 M）处理小鼠Th 2细胞系D10.G4.1细胞，然后用PMA（佛波醇12肉豆蔻酸酯13-乙酸酯）加离子霉素或α CD 3活化。然后通过酶联免疫吸附试验（ELISA）和半定量逆转录聚合酶链反应（RT-PCR）测定IL-13的产生水平。用组胺受体拮抗剂吡拉明、雷尼替丁、西咪替丁和硫代哌丁胺预处理细胞，以确定组胺受体的参与。在加入组胺之前，还用蛋白激酶A（PKA）抑制剂N-[2-（甲基氨基乙基）]-5-异喹啉-磺酰胺（H-8）和腺苷环3′5′-硫代磷酸酯的Rp-非对映体（Rp-cAMPS）以及Janus激酶-信号转导子和转录激活子（Jak-STAT）抑制剂tyrphostin AG 490预处理细胞。H-8是PKA催化亚基的抑制剂，而Rp-cAMPS是PKA调节亚基的抑制剂。Tyrphostin是Jak 2、Jak 3、STAT 1、STAT 3和STAT 5的抑制剂。最后，用IL-12预处理细胞，IL-12是已知抑制STAT 6 DNA结合的单核因子。我们发现，组胺剂量依赖性地增强IL-13的分泌和mRNA水平的Th 2细胞通过H1和H2受体。用H-8、Rp-cAMPS和tyrphostin预处理细胞阻止组胺诱导的IL-13的分泌和转录。同样，用IL-12预处理Th 2细胞也逆转组胺对IL-13分泌的作用，从刺激变为抑制。这些观察结果表明PKA和Jak-STAT通路在组胺介导的IL-13分泌和转录升高中的作用。
Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10−8–10−4M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or αCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3′5′-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STAT1, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.