Ask about this productRelated genes to: RANTES protein
- Gene:
- CCL5 NIH gene
- Name:
- C-C motif chemokine ligand 5
- Previous symbol:
- D17S136E, SCYA5
- Synonyms:
- RANTES, SISd, TCP228, MGC17164
- Chromosome:
- 17q12
- Locus Type:
- gene with protein product
- Date approved:
- 1990-07-05
- Date modifiied:
- 2016-03-01
Related products to: RANTES protein
Related articles to: RANTES protein
- Avian influenza virus primarily invades the respiratory mucosa, necessitating the establishment of a robust mucosal secretory IgA (sIgA) barrier. However, the efficacy of avian mucosal vaccines is often hindered by inefficient antigen uptake and immune tolerance. Consequently, modern vaccine strategies focus on active targeting delivery, immune microenvironment remodeling, and activation of multifaceted immune responses. The immunogenicity and molecular mechanisms of a novel Salmonella-delivered self-amplifying RNA (saRNA) vector platform were evaluated in this study. This platform integrates bacterial surface display of a dendritic cell (DC)-targeting nanobody (Nb-phage54 via LppOmpA) with co-expression of molecular adjuvants against H9N2 influenza. The expression of HA1 and NA antigens from recombinant plasmids (pYL673, pYL679, and pYL681) was confirmed using confocal microscopy and Western blot analysis. In vitro assays revealed that the Nb-mediated targeting strain (S673) significantly increased invasion efficiency into bone marrow-derived dendritic cells and up-regulated the transcription of CCL5, CCR7, CD83, and CD86, effectively promoting DC maturation. Transcriptomic analysis (RNA-seq) revealed divergent mechanisms among vaccine candidates. The non-targeting group (S615) primarily activated antiviral innate pathways, such as JAK-STAT, whereas the targeting group (S673) significantly improved antigen processing, presentation, and natural killer cell-mediated cytotoxicity. Moreover, the adjuvant-integrated groups, S679 (CpG) and S681 (FliC), specifically triggered Toll-like receptor-21 (TLR21) and TLR5 signaling cascades by increasing cell adhesion, phagocytosis, and transmembrane signal transduction. Animal trials revealed that the targeted adjuvant vectors (S679 and S681) significantly elevated serum IgG and intestinal mucosal sIgA titers in chickens. The S679 group excelled in stimulating lymphocyte proliferation and secreting interferon-gamma and interleukin-4, indicating a potent Th1/Th2 balanced response. Challenge experiments with H9N2 virus confirmed that S679 and S681 effectively mitigated weight loss, shortened the viral shedding window, reduced viral loads in the lungs and trachea, and significantly alleviated respiratory pathological damage and inflammation. The DC-targeting saRNA-Salmonella vector developed in this study, particularly when synergized with CpG or FliC adjuvants, induced robust systemic, mucosal, and cellular immunity by activating specific intracellular signaling cascades. These findings demonstrate that this platform is a highly effective and promising candidate strategy for preventing and controlling H9N2 avian influenza. - Source: PubMed
Publication date: 2026/04/24
Wang MingyueGao YupengZhang YuxiYang TianruiZhang YuhangSun YanGuo QiyuZhang GeruiGong JinshuoWang ZhannanWang ChunfengJiang Yanlong - This study explored the effect and dual-targeting mechanism of total lignans from flower buds of Magnolia biondii Pamp. (TLFM) against AD. - Source: PubMed
Publication date: 2026/04/22
Yan MengdanYu WenchaoCheng MeiyuWu LonglongHan LinhangChen KaixianLi YimingZhang QingguangZhang LiuqiangQian Fei - , the spirochetal agent of Lyme disease, has a large array of lipoproteins that play a significant role in mediating host-pathogen interactions within ticks and vertebrates. While prior work has established that borrelial lipoproteins (LP) modulate immune signaling pathways, the broader transcriptional and proteomic programs induced by these molecules in macrophages are unclear. Here, we used integrated multi-omics approaches to characterize host signaling pathways activated specifically by purified borrelial lipoproteins in murine bone marrow derived macrophages (BMDMs). Single-cell RNA-Seq (scRNA-Seq) performed on BMDMs treated with various concentrations of borrelial lipoproteins revealed macrophage subsets within the BMDMs. Differential expression analysis showed that genes encoding various receptors, type I IFN-stimulated genes, signaling chemokines are upregulated while mitochondrial and ribosomal genes are downregulated in BMDMs in response to lipoproteins. Unbiased proteomics analysis of lysates of BMDMs treated with lipoproteins corroborated several of these findings. Notably, dual specificity phosphatase 1 () gene was upregulated during the early stages of BMDM exposure to LP. Pharmacological inhibition with benzylidene-3-cyclohexylamino-1-indanone hydrochloride (BCI), an inhibitor of both DUSP1 and 6 prior to exposure to LP, demonstrated that DUSP1 negatively regulates NLRP3-mediated pro-inflammatory signaling and positively regulates the expression of interferon-stimulated genes and those encoding , , and . Using human monocytic reporter cell lines, we showed MyD88- and IKK-dependent pathways contribute to mitochondrial alterations upon stimulation with lipoproteins. Extracellular flux analysis using the Seahorse assay revealed decreased oxygen consumption rate (OCR) and increased extracellular acidification rate (ECAR), indicating time-dependent metabolic reprogramming and a shift toward a glycolytic, pro-inflammatory metabolic state in BMDMs following LP stimulation. Collectively, these findings define signaling networks, regulatory nodes and metabolic alterations induced by borrelial lipoproteins in macrophages and highlight DUSP1 as a key modulator of lipoprotein-driven innate immune responses. This work provides a mechanistic framework for understanding how borrelial lipoproteins shape macrophage signaling, independent of the broader complexity of infection with intact pathogen. - Source: PubMed
Publication date: 2026/04/07
Kumaresan VenkateshPahari SusantaHung Chiung-YuHermann Brian PSchlesinger Larry SSeshu J - Remarkable progress has been made in cancer immunotherapy, partly because of the development of immune checkpoint inhibitors. However, their efficacy varies across cancer types, with limited response observed in solid tumors, such as hepatocellular carcinoma (HCC). The primary cause of this low efficacy is insufficient infiltration of effector cells, such as cytotoxic CD8 T cells, into the tumor tissue. This study investigated whether recombinant interleukin (rIL)-2, rIL-18, and antiprogrammed cell death-ligand 1 (αPD-L1) antibody (Ab) could serve as novel immunotherapies for HCC. Multidrug resistance gene 2-deficient mice, a spontaneously occurring liver cancer model associated with aging, were administered rIL-2, rIL-18, and αPD-L1Ab. Antitumor effects were evaluated using computed tomography and serum alpha-fetoprotein levels. Significant tumor shrinkage was observed in the rIL-2+rIL-18+αPD-L1Ab group, but not in the rIL-2+αPD-L1Ab or rIL-18+αPD-L1Ab groups. Concurrent administration of αCD8-neutralizing antibody abolished the antitumor effect, indicating CD8 T-cell dependency. Spatial gene expression profiling revealed that intratumoral CD8 effector T cells express and secrete CCL5 after treatment, promoting CD8 T-cell mobilization to the liver and enhancing antitumor efficacy. Pretreatment with a CCL5 neutralizing antibody suppressed CD8+ cell infiltration into the tumor, eliminating the antitumor effect. The triple combination therapy used in this study promotes the infiltration and maintenance of CD8 T cells in the liver, suggesting a promising new immunotherapy for HCC. - Source: PubMed
Publication date: 2026/04/15
Kimura MasamichiYamaji KenzaburoHarada KenichiKawaji HideyaImamura JunOkamura HarukiTanaka YoshimasaKohara MichinoriKimura Kiminori - Focal adhesion kinase (FAK) is overexpressed and hyperactivated in triple-negative breast cancer, driving tumor aggressiveness and cancer stem cell-mediated therapy resistance. Therefore, targeting FAK signalling represents a promising therapeutic strategy. In this study, a series of indole and bis-indole-1,2,4-triazoles were synthesized and evaluated as anti-TNBC agents targeting FAK. Compounds 3c, 4c, and 5c displayed potent cytotoxicity (IC₅₀ = 41-77 µg/mL) with minimal toxicity to normal cells, outperforming precursor compound 2. Wound-healing assay revealed significant inhibition of cell migration, particularly by 4c. Cell cycle analysis revealed that 4c induced S-phase arrest in MCF-7 cells and G1-phase arrest in MDA-MB-231 cells, accompanied by significant apoptosis. In MDA-MB-231 cells, 4c triggered extensive total apoptosis (90.84%) with minimal necrosis. Gene expression studies demonstrated that 4c markedly downregulated PTK2 (FAK), CCL5, and BCL2, while upregulating CASP3, highlighting its dual role as FAK inhibitor and apoptosis inducer. Importantly, 4c efficiently suppressed FAK protein expression (61.3%) in TNBC, compared to the FAK inhibitor GSK-2256098 (70.7%). In vivo toxicity assessment confirmed good tolerability in mice without profound hepatic or renal impairments, while docking and ADMET analyses confirmed strong FAK binding affinity, and favourable pharmacokinetics of 4c. Collectively, 4c emerges as a promising FAK-targeted candidate for TNBC therapy. - Source: PubMed
Publication date: 2026/04/22
Abd El Salam Hayam AAbu-Shahba NourhanIbrahim Fouad GhadhaMahmoud MarwaMostafa Eslam AAbozeid Mona A MAbo-Salem Heba MAzouz Rasha A M