Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cell (DC) vaccine is a potent immunotherapeutic approach for cancer treatment, but the clinical efficacy needs to be improved. In this study, we evaluated the combinational effect of Toll-like receptor 7 (TLR7) agonist Imiquimod and BM-DC vaccine against mouse melanoma and explored the potential mechanisms. We found that topical application of Imiquimod cream caused skin inflammation and enhanced exogenous BM-DC homing to draining lymph nodes. Imiquimod treatment enhanced DC vaccine efficacy against B16-OVA melanoma. The combinational modality enhanced cytotoxicity of splenic lymphocyte to tumor cells and inhibited CD4+FOXP3+Treg cell production. TLR7 mRNA expression was confirmed in both MC/9 mast cells and DCs. MC/9 cells treated by R837 (soluble form of Imiquimod) enhanced CD80, CD86, MHC-II and CCR7 expression on DCs. R837 inhibited B16-OVA cell growth in vitro. Our findings suggest that Imiquimod can be used as a potent adjuvant in the formulation of a DC-based tumor fighting vaccine. The mechanisms underlying these effects of Imiquimod are related with enhanced DC homing to DLNs, inhibition of Treg's production, direct tumor cell toxicity and synergistic function with mast cell in enhancing DC activation.
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PMID:Imiquimod enhances the potency of an exogenous BM-DC based vaccine against mouse melanoma. 3014 66

Imiquimod (Imiq) is a synthetic imizoquinoline compound which can act on Toll-like receptor (TLR)7 and transduce signals involved in cell activation. We investigated the role of Imiq on contact hypersensitivity (CHS) and explored the potential mechanisms of mast cells involved in the process. Topical application of Imiq cream augmented DNFB mediated CHS in C57BL/6 mice. Imiq application induced skin inflammation and increased the number of dendritic cells (DCs) in the draining lymph nodes (DLNs). The splenic cell proliferation to DNBS in DNFB and Imiq treated mice was greater than that in mice of DNFB treatment alone. Peritoneal cell-derived mast cells (PCMCs) expressed TLR7 mRNA. The results from toluidine blue staining for mast cells and histamine detection indicated that Imiq alone did not induce mast cell degranulation while Imiq plus DNFB significantly induced mast cell degranulation. Cromolyn, pyrilamine and cimetidine attenuated CHS reaction induced by Imiq. Our findings suggest that Imiq could augment the intensity of CHS reaction. The mechanisms underlying the effect may relate to histamine release by mast cells and induction of DC homing to DLNs. Blocking histamine action in early time of allergen contact is beneficial to the alleviation of CHS.
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PMID:Imiquimod enhances DNFB mediated contact hypersensitivity in mice. 3100 38