Complement C1q regulates LPS‐induced cytokine production in bone marrow‐derived dendritic cells
Complement C1q regulates LPS‐induced cytokine production in bone marrow‐derived dendritic cells
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DOI：
10.1002/eji.200324026
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发表时间：
2004-01
影响因子：
5.4
通讯作者：
Masahide Yamada;K. Oritani;T. Kaisho;J. Ishikawa;H. Yoshida;Isao Takahashi;Shin-ichiro Kawamoto;N. Ishida;H. Ujiie;H. Masaie;M. Botto;Y. Tomiyama;Y. Matsuzawa
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文献类型：
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作者：
Masahide Yamada;K. Oritani;T. Kaisho;J. Ishikawa;H. Yoshida;Isao Takahashi;Shin-ichiro Kawamoto;N. Ishida;H. Ujiie;H. Masaie;M. Botto;Y. Tomiyama;Y. Matsuzawa
我们在这里表明，C1 q抑制LPS刺激的小鼠骨髓来源的树突状细胞（BMDC）中IL-12 p40的产生。腹腔注射LPS后，C1 q缺陷型小鼠的血清IL-12 p40浓度高于野生型小鼠。由于C1 q的球状头部（gC 1 q）和C1 q的胶原样区域（cC 1 q）都不能抑制LPS诱导的IL-12 p40产生，因此抑制可能需要gC 1 q和cC 1 q和/或天然C1 q的某些特定构象。虽然C1 q不影响Toll样受体4（TLR 4）、MD-2和髓样分化因子88（MyD 88）的mRNA表达，但经C1 q处理的BMDC在LPS刺激后显示NF-κB活性降低，p38、c-Jun N-末端激酶和细胞外信号调节激酶磷酸化延迟。CpG寡脱氧核苷酸诱导的IL-12 p40和TNF-α产生（另一种MyD 88依赖性TLR介导的信号）也被C1 q处理抑制。因此，C1 q可能抑制TLR介导信号中的MyD 88依赖性通路。相反，C1 q未能抑制MyD 88缺陷小鼠中BMDC上对LPS或LPS诱导的CD 40和CD 86表达作出反应的B细胞的集落形成，表明C1 q对MyD 88非依赖性途径的抑制作用可能有限。综上所述，C1 q可能通过修饰入侵病原体与TLR之间相互作用介导的信号来调节先天性和适应性免疫系统。
We show here that C1q suppresses IL‐12p40 production in LPS‐stimulated murine bone marrow‐derived dendritic cells (BMDC). Serum IL‐12p40 concentration of C1q‐deficient mice was higher than that of wild‐type mice after intraperitoneal LPS‐injection. Because neither globular head of C1q (gC1q) nor collagen‐like region of C1q (cC1q) failed to suppress LPS‐induced IL‐12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll‐like receptor 4 (TLR4), MD‐2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF‐κB and the delayed phosphorylation of p38, c‐Jun N‐terminal kinase, and extracellular signal‐regulated kinase after LPS‐stimulation. CpG oligodeoxynucleotide‐induced IL‐12p40 and TNF‐α production, another MyD88‐dependent TLR‐mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88‐dependent pathway in TLR‐mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS‐induced CD40 and CD86 expression on BMDC in MyD88‐deficient mice, indicating that inhibitory effects of C1q on MyD88‐independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signalsmediated by interactions between invading pathogens and TLR.