Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myeloid-derived suppressor cells (MDSCs) play an immunosuppressive role in the pathogenesis of inflammatory diseases. CD180, a TLR-like protein, can regulate the proliferation and activation of immune cells. However, the roles of CD180 in regulating the accumulation and function of MDSCs have not been investigated. Here, we found that, compared with non-treated controls, the expression of CD180 was significantly elevated in MDSCs, especially granulocytic MDSCs (G-MDSCs), from mice challenged with lipopolysaccharide (LPS). Ligation of CD180 by the anti-CD180 antibody not only blocked the expansion of MDSCs by preventing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), but also reduced the immunosuppressive activity of MDSCs on M1 macrophage polarization through inhibition of Arg-1 expression in vitro. In vivo studies showed that injection of anti-CD180 antibody significantly aggravated pathological lesions in mice challenged with LPS. Furthermore, injection of anti-CD180 antibody inhibited the accumulation of G-MDSCs in mice challenged with LPS and reduced the immunosuppressive activity of G-MDSCs on M1 macrophage polarization. Based on these findings, we conclude that ligation of CD180 contributes to the pathogenesis of endotoxic shock by inhibiting the accumulation and immunosuppressive activity of G-MDSCs, thus providing insight into the function of CD180 in inflammatory diseases.
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PMID:Ligation of CD180 contributes to endotoxic shock by regulating the accumulation and immunosuppressive activity of myeloid-derived suppressor cells through STAT3. 3055

Multiple myeloma (MM) is among the most intractable of malignancies and is characterized by uncontrolled growth of malignant plasma cells in the bone marrow (BM). Elucidation of the mechanisms underlying cell adhesion-mediated drug resistance (CAM-DR) may prolong remission and ultimately improve the survival of MM patients. Toward this goal, we identified trimethylation of histone H3 at lysine-27 (H3K27me3) as a critical histone modification associated with CAM-DR. Cell adhesion counteracted drug-induced hypermethylation of H3K27 via inhibiting phosphorylation of enhancer of zeste homolog 2 (EZH2), and promoted sustained expression of anti-apoptotic genes. In addition, we found that CD180, a non-canonical lipopolysaccharide (LPS) receptor, was markedly up-regulated in response to adherence and/or hypoxic conditions. Bacterial LPS enhanced the growth of MM cells both in vitro and in vivo, correlating with expression of CD180. Promoter analyses identified Ikaros (IKZF1) as a pivotal transcriptional activator of the CD180 gene; expression of CD180 was activated via cell adhesion- and/or hypoxia-mediated increases in IKZF1 expression. Administration of lenalidomide prevented the LPS-triggered activation of MM cells by targeting CD180. Taken together, our results suggest that lenalidomide-mediated prevention of LPS-triggered disease progression may be an effective means for prolonging survival in patients with MM.
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PMID:[Toll-like receptor CD180 and the bone marrow microenvironment as therapeutic targets in multiple myeloma]. 3275 72


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