PMID- 14971048 OWN - NLM STAT- MEDLINE DCOM- 20040316 LR - 20061115 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 34 IP - 1 DP - 2004 Jan TI - Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells. PG - 221-30 AB - 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-kappaB 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-alpha 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 signals mediated by interactions between invading pathogens and TLR. FAU - Yamada, Masahide AU - Yamada M AD - Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan. FAU - Oritani, Kenji AU - Oritani K FAU - Kaisho, Tsuneyasu AU - Kaisho T FAU - Ishikawa, Jun AU - Ishikawa J FAU - Yoshida, Hitoshi AU - Yoshida H FAU - Takahashi, Isao AU - Takahashi I FAU - Kawamoto, Shinichirou AU - Kawamoto S FAU - Ishida, Naoko AU - Ishida N FAU - Ujiie, Hidetoshi AU - Ujiie H FAU - Masaie, Hiroaki AU - Masaie H FAU - Botto, Marina AU - Botto M FAU - Tomiyama, Yoshiaki AU - Tomiyama Y FAU - Matsuzawa, Yuji AU - Matsuzawa Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antigens, Differentiation) RN - 0 (Antigens, Ly) RN - 0 (Cytokines) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Lipopolysaccharides) RN - 0 (Ly96 protein, mouse) RN - 0 (Lymphocyte Antigen 96) RN - 0 (Membrane Glycoproteins) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Protein Subunits) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Immunologic) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - 187348-17-0 (Interleukin-12) RN - 80295-33-6 (Complement C1q) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Antigens, Differentiation/genetics/metabolism MH - Antigens, Ly/genetics/metabolism MH - Bone Marrow Cells/*metabolism MH - Complement C1q/*metabolism MH - Cytokines/*biosynthesis MH - Dendritic Cells/*metabolism MH - Female MH - Interleukin-12/biosynthesis MH - Interleukin-12 Subunit p40 MH - Lipopolysaccharides/metabolism MH - Lymphocyte Antigen 96 MH - Membrane Glycoproteins/genetics/metabolism MH - Mice MH - Myeloid Differentiation Factor 88 MH - Protein Subunits/biosynthesis MH - RNA, Messenger/metabolism MH - Receptors, Cell Surface/genetics/metabolism MH - Receptors, Immunologic/genetics/metabolism MH - Signal Transduction/physiology MH - Toll-Like Receptor 4 MH - Toll-Like Receptors EDAT- 2004/02/19 05:00 MHDA- 2004/03/18 05:00 CRDT- 2004/02/19 05:00 PHST- 2004/02/19 05:00 [pubmed] PHST- 2004/03/18 05:00 [medline] PHST- 2004/02/19 05:00 [entrez] AID - 10.1002/eji.200324026 [doi] PST - ppublish SO - Eur J Immunol. 2004 Jan;34(1):221-30. doi: 10.1002/eji.200324026.