Tongue RNA expression after oropharyngeal candidiasis in mice deficient in CCL28
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE165545 | GEO | 2024/01/25
REPOSITORIES: GEO
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Project description:Tongue RNA expression after oropharyngeal candidiasis in mice deficient in CCL28
| PRJNA694936 | ENA
Project description:Candida albicans is a commensal organism that causes life-threatening or life-altering opportunistic infections. Treatment of Candida infections is limited by the paucity of antifungal drug classes. Naturally occurring antimicrobial peptides are promising agents for drug development. CCL28 is a CC chemokine that is abundant in saliva and has in vitro antimicrobial activity. In this study, we examine the in vivo Candida killing capacity of CCL28 in oropharyngeal candidiasis as well as the spectrum and mechanism of anti-Candida activity. In the mouse model of oropharyngeal candidiasis, application of wild-type CCL28 reduces oral fungal burden in severely immunodeficient mice without causing excessive inflammation or altering tissue neutrophil recruitment. CCL28 is effective against multiple clinical strains of C. albicans Polyamine protein transporters are not required for CCL28 anti-Candida activity. Both structured and unstructured CCL28 proteins show rapid and sustained fungicidal activity that is superior to that of clinical antifungal agents. Application of wild-type CCL28 to C. albicans results in membrane disruption as measured by solute movement, enzyme leakage, and induction of negative Gaussian curvature on model membranes. Membrane disruption is reduced in CCL28 lacking the functional C-terminal tail. Our results strongly suggest that CCL28 can exert antifungal activity in part via membrane permeation and has potential for development as an anti-Candida therapeutic agent without inflammatory side effects.
| S-EPMC7526824 | biostudies-literature
Project description:Candida albicans, the causative agent of mucosal infections including oropharyngeal candidiasis (OPC) as well as bloodstream infections is becoming increasingly resistant to existing treatment options. In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat off label diseases is a promising strategy. C. albicans requires environmental iron for survival and virulence while host nutritional immunity deploys iron-binding proteins to sequester iron and reduce fungal growth. Here we evaluated the role of iron-limitation using Deferasirox (an FDA approved iron chelator for treatment of patients with iron overload) during murine OPC; and assessed Deferasirox-treated C. albicans for its interaction with human oral epithelial (OE), neutrophils, and antimicrobial peptides. Therapeutic Deferasirox treatment significantly reduced salivary iron levels while a non-significant reduction in fungal burden was observed. Preventive treatment that allowed for two additional days of drug administration in our murine model, resulted in significant reduction of C. albicans colony forming units (CFU)/g of tongue tissue, a significant reduction in salivary iron levels, and significantly reduced neutrophil-mediated inflammation. C. albicans harvested from tongues of animals undergoing preventive treatment had differential expression of 106 genes, including those involved in iron metabolism, adhesion, and response to host innate immunity. Moreover, Deferasirox-treated C. albicans cells had two-fold reduction in survival in neutrophil phagosomes (with greater susceptibility to oxidative stress); and reduced adhesion and invasion of OE cells, in vitro. Thus Deferasirox treatment has the potential to alleviate OPC by affecting C. albicans gene expression and reducing virulence
2018-12-04 | GSE123277 | GEO
Project description:Secretome-based therapies targeting angiogenesis are promising in ischemic heart disease (IHD). The effects of Chemokine C-C motif ligand (CCL) 28 on IHD remain unclear. This study investigated the role of CCL28 in angiogenesis in IHD. The myocardial infarction (MI) and hindlimb ischemia (HI) models were constructed on male wild-type and CCL28-knockout mice. AAV9-TIE1-sh-CCR10 induced endothelial specific CCR10 deficiency in mice by tail vein injection. Recombinant CCL28 protein was used to treat MI and HI in wild-type and db/db mice. Serum levels of CCL28 were evaluated in a cohort of 416 consecutive chronic total occlusions (CTO) patients. The upregulated CCL28/ C-C motif receptor (CCR)10 axis was observed in myocardial and hindlimb ischemia. Additionally, CCL28 was mainly secreted by macrophages and CCR10 was highly expressed in endothelial cells (ECs). Compared to CCR10- ECs, CCR10+ ECs exhibited robust proangiogenic capacity, which are induced by CCL28 through the CCR10/ERK/SOX5 positive feedback signaling. Deletion of CCL28 results in impaired angiogenesis in the ischemic models while the use of recombinant CCL28 protein has therapeutic potential for myocardial and hindlimb ischemia, including in diabetes. Endothelial specific CCR10 deficiency impairs angiogenesis and blocks the therapeutic effect of rCCL28 in the myocardial and hindlimb ischemia. Serum CCL28 levels exhibited the predictive effect on coronary collateral vessels (CCV) in CTO patients. CCR10+ endothelial cells (ECs) are characterized with the enhanced proangiogenic capacity and beneficial for angiogenesis. CCL28 promotes angiogenesis by increasing CCR10+ ECs via the CCR10/ERK/SOX5 positive feedback signaling. This study highlights the angiogenic role of CCL28 and recombinant CCL28 protein might be a potential therapeutic option to attenuate myocardial and hindlimb ischemia, including in diabetes.
2025-09-09 | GSE290928 | GEO
Project description:We identified chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor for HSPCs with the ability to enhance the proliferation potential of fetal, neonatal and adult CD34+ HSPCs after one week of culture in serum-free medium containing limiting stem cell factor (SCF) concentrations. Importantly, CCL28 could increase the progenitor potential of CB- and bone marrow (BM) derived CD34+ cells as measured by colony assays. Furthermore, treatment of CB CD34hiCD38loCD90+CD45RA- cells with CCL28 significantly enhanced the ability of the cells to long-term repopulate immunodeficient mice compared to SCF-treated cultures. Our findings show that CCL28 is a potent growth factor for human HSCs and suggest that it should be further exploited in clinical strategies for ex vivo expansion. Human CD34+CD38-CD45RAlowCD90+ cord blood cells were cultured in vitro for 18 hrs with CCL28 and SCF or SCF alone.
2013-01-01 | E-GEOD-35374 | biostudies-arrayexpress
Project description:We identified chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor for HSPCs with the ability to enhance the proliferation potential of fetal, neonatal and adult CD34+ HSPCs after one week of culture in serum-free medium containing limiting stem cell factor (SCF) concentrations. Importantly, CCL28 could increase the progenitor potential of CB- and bone marrow (BM) derived CD34+ cells as measured by colony assays. Furthermore, treatment of CB CD34hiCD38loCD90+CD45RA- cells with CCL28 significantly enhanced the ability of the cells to long-term repopulate immunodeficient mice compared to SCF-treated cultures. Our findings show that CCL28 is a potent growth factor for human HSCs and suggest that it should be further exploited in clinical strategies for ex vivo expansion.
2013-01-01 | GSE35374 | GEO
Project description:The ability to taste is critical for animal nutrition and toxin deterrence. The majority of research on taste bud development and regeneration is in mice, where taste buds are located within specialized papillae on the tongue. However, taste buds in fish and amphibians, such as axolotls (Ambystoma mexicanum), are not housed in papillae, rather they are within the pharyngeal epithelium. This simplified tissue level organization, along with the ability of cultured oropharyngeal explants from early embryos to produce taste buds on the same time-line as embryos, make the axolotl an excellent model to identify molecules specifically involved in taste bud cell differentiation. In this study, we performed de novo transcriptomic analysis on RNA sequences from three different stages of oropharyngeal explants: stages 37/38, 39, and 41. RNA-seq data from 17 total samples representing these stages were pooled to generate de novo assemblie(s) of the transcriptome using a Trinity pipeline. Raw reads and the assembly were uploaded to Mendeley (doi:10.17632/tvxh3jm83m.1). From 27.9Gb of raw sequences, we identified 21,244 transcripts. To our knowledge, this study provides the first published assembly of axolotl oropharyngeal endoderm explants. This RNA-seq data and transcriptome assembly provide information on genes expressed in the oropharyngeal endoderm and will be valuable in the identification of taste bud development genes.
2020-06-02 | GSE151535 | GEO
Project description:To discover novel growth factors for hematopoietic stem- and progenitor cells (HSPCs), we have assessed cytokine responses of cord blood (CB)-derived CD34+ cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins. Microarrays are used to compare the expression profiles of HSPCs expanded in SCF, TPO and CCL28 respectively. HSPCs were cultured in Serum-Free Expansion Medium with SCF, SCF + TPO, and SCF + CCL28 respectively, and hybridised microarrays in triplicate.
2013-06-03 | E-GEOD-45136 | biostudies-arrayexpress
Project description:Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.
2023-08-28 | GSE241702 | GEO
Project description:Iron Chelator Deferasirox Reduces Candida albicans Invasion of Oral Epithelial Cells and Infection Levels in Murine Oropharyngeal Candidiasis
| PRJNA508086 | ENA