Promotion of the inflammatory response in mid colon of complement component 3 knockout mice.
Promotion of the inflammatory response in mid colon of complement component 3 knockout mice.
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DOI：
10.1038/s41598-022-05708-8
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发表时间：
2022-02-01
影响因子：
4.6
通讯作者：
Hwang DY
中科院分区：
文献类型：
--
作者：
Choi YJ;Kim JE;Lee SJ;Gong JE;Jin YJ;Lee H;Hwang DY
为了确定补体成分3(C3)缺乏是否影响其受体下游介导的炎症反应，本研究检测了C3基因敲除(KO)小鼠中结肠中诱导型一氧化氮合酶(INOS)介导的环氧合酶-2(COX-2)诱导途径、炎症体途径、核因子-κB(NF-κB)激活和炎性细胞因子表达的变化。INOS介导的COX-2诱导途径的关键成分的表达显著增强，丝裂原活化蛋白(MAP)激酶成员的磷酸化也显著增强。在C3KO小鼠中也观察到了类似的炎症体蛋白表达水平的增加。此外，与WT小鼠相比，C3KO小鼠的NF-κB和κB-α抑制因子(IκB-α)的磷酸化水平显著增强，总体表现为肿瘤坏死因子、IL-6和IL-1α的表达增加。然而，尽管中性粒细胞的髓过氧化物酶(MPO)活性略有升高，但C3KO小鼠E-钙粘素、紧密连接通道和离子通道的表达水平较低。综上所述，本研究结果表明，C3缺乏可通过激活诱导型一氧化氮合酶介导的COX-2诱导通路、含有半胱氨酸酶征募结构域(AsC)-炎症体通路和NF-κB信号通路的凋亡相关的SPECK样蛋白，以及增强炎症细胞因子的表达来促进C3KO小鼠中段结肠的炎症反应。
To determine whether complement component 3 (C3) deficiency affects its receptor downstream-mediated inflammatory response, the current study was undertaken to measure alterations in the inducible nitric oxide synthase (iNOS)‑mediated cyclooxygenase‑2 (COX‑2) induction pathway, inflammasome pathway, nuclear factor-κB (NF-κB) activation, and inflammatory cytokine expressions in the mid colon of C3 knockout (KO) mice. Significant enhancement was observed in expressions of key components of the iNOS‑mediated COX‑2 induction pathway, and in the phosphorylation of mitogen‑activated protein (MAP) kinase members. A similar pattern of increase was also observed in the expression levels of inflammasome proteins in C3 KO mice. Moreover, compared to WT mice, C3 KO mice showed remarkably enhanced phosphorylation of NF-κB and Inhibitor of κB-α (IκB-α), which was reflected in entirety as increased expressions of Tumor necrosis factor (TNF), IL-6 and IL-1α. However, the levels of E-cadherin, tight junction channels and ion channels expressions were lower in the C3 KO mice, although myeloperoxidase (MPO) activity for neutrophils was slightly increased. Taken together, results of the current study indicate that C3 deficiency promotes inflammatory responses in the mid colon of C3 KO mice through activation of the iNOS‑mediated COX‑2 induction pathway, Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-inflammasome pathway and NF-κB signaling pathway, and the enhancement of inflammatory cytokine expressions.
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DOI：
10.2119/molmed.2010.00149
发表时间：
2011-03
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Ehrnthaller C;Ignatius A;Gebhard F;Huber-Lang M
通讯作者：
Huber-Lang M
影响因子：
4
作者：
Choi YJ;Kim JE;Lee SJ;Gong JE;Son HJ;Hong JT;Hwang DY
通讯作者：
Hwang DY
影响因子：
17.1
作者：
Arrieta, Marie-Claire;Stiemsma, Leah T.;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael
DOI：
10.1159/000463070
发表时间：
1989-01-01
期刊：
COMPLEMENT AND INFLAMMATION
影响因子：
--
作者：
DALMASSO, AP;FALK, RJ;RAIJ, L
通讯作者：
RAIJ, L