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Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

100%

Zhong W., Fei M., Zhu Y., Zhang X.

Cellular and Molecular Biology Letters

2009

tom 14

nr 4

587-608

Dendritic cells (DC) are professional antigen-presenting cells capable of initiating primary immune responses. They have been intensively studied and are used in both basic immunology research and clinical immunotherapy. However, the genetic pathways leading to DC differentiation and maturation remain poorly understood. Using focused microarrays with oligonucletotide probes for 120 genes encoding co-stimulatory molecules, chemokines, chemokine receptors, cytokines, cytokine receptors, TLRs, and several other related molecules, we analyzed the kinetics of gene expression for the overall differentiation process of monocytes into mature DC. In parallel, we compared the transcriptional profiles in DC maturation in the presence of LPS, TNF-α or trimeric CD40L. We found similar transcriptional profiles for early immature DC and immature DC, respectively generated by culturing monocytes with GM-CSF and IL-4 for three or six days. We identified sets of common and stimuli-specific genes, the expression of which changed following stimulation with LPS, TNF-α or CD40L. A dynamic analysis of the entire DC differentiation and maturation process showed that some important inflammatory and constitutive chemokines are transcribed in both immature and mature DC. The correlative expression kinetics of the gene pairs IL1R1/IL1R2, IL15/IL15RA, DC-SIGN/ICAM-2 and DC-SIGN/ICAM-3 imply that they all play crucial roles in mediating DC functions. Thus, our analysis with focused microarrays shed light on the transcriptional kinetics of DC differentiation and maturation, and this method may also prove useful for identifying novel marker genes involved in DC functions.

Hypoxia promotes the migration and invasion of human hepatocarcinoma cells through the HIF-1α–IL-8–Akt axis

76%

Fei M., Guan J., Xue T., Qin L., Tang C., Gong H., Feng W.

Cellular and Molecular Biology Letters

2018

tom 23

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. The 5-year survival rate remains low despite considerable research into treatments of HCC, including surgery, radiotherapy and chemotherapy. Many mechanisms within HCC still require investigation, including the influence of hypoxia, which has a crucial role in many cancers and is associated with metastasis. Hypoxia inducible factor-1α (HIF-1α) is known to regulate the expression of many chemokines, including interleukin-8 (IL-8), which is associated with tumor metastasis. Although many studies have reported that HIF-1α is associated with HCC migration and invasion, the underlying mechanisms remain unknown. Methods: The expression level of HIF-1α was determined in HCC cells. The correlation of IL-8 and HIF-1α expressions was assessed via knockdown of HIF-1α. HCC cells were also used to assess the influence of HIF-1α on HCC cell migration and invasion. LY294002, an inhibitor of the Akt pathway, was used to confirm the associated signaling pathways. Results: We observed a significant attenuation of cell migration and invasion after silencing of HIF-1α. Exogenously expressing IL-8 restored migration and invasion. Akt was found to be involved in this process. Conclusion: Hypoxia promotes HCC cell migration and invasion through the HIF-1α–IL8–Akt axis.

Ograniczanie wyników

2 Cellular and Molecular Biology Letters

2 Fei M.

1 Feng W.

1 Gong H.

1 Guan J.

1 Qin L.

1 Tang C.

1 Xue T.

1 Zhang X.

1 Zhong W.

1 Zhu Y.

1 2018

1 2009

Wyniki wyszukiwania

Transcriptional profiles during the differentiation and maturation of monocyte-derived dendritic cells, analyzed using focused microarrays

Hypoxia promotes the migration and invasion of human hepatocarcinoma cells through the HIF-1α–IL-8–Akt axis