Increased C-C Chemokine Receptor 2 Gene Expression in Monocytes of Severe Obstructive Sleep Apnea Patients and under Intermittent Hypoxia

Chuang, Li‐Pang; Chen, Ning‐Hung; Lin, Shih‐Wei; Chang, Ying-Ling; Liao, Hsiang‐Ruei; Lin, Yu‐Sheng; Chao, I-Ju; Lin, Yuling; Pang, Jong‐Hwei S.

doi:10.1371/journal.pone.0113304

Cited by 16 publications

(24 citation statements)

References 49 publications

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“…Similar to adipocytes, when other cell types underwent a protocol of IH with defined pO 2 in vitro, the results were consistent with other IH models. For instance, gene expression profiles of neutrophils, monocytes, and airway epithelial cells all matched the results found in OSA patients, further hinting at the role of inflammation in the pathophysiology of the disease (123)(124)(125)(126). Constant monitoring of pO 2 of the PC12 cell line confirmed the central role of HIF-1α in the molecular response to IH (127).…”

Section: Intermittent Hypoxiasupporting

confidence: 60%

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

Pavlacky

Polàk

2020

Front. Endocrinol.

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Hypoxia is characterized as insufficient oxygen delivery to tissues and cells in the body and is prevalent in many human physiology processes and diseases. Thus, it is an attractive state to experimentally study to understand its inner mechanisms as well as to develop and test therapies against pathological conditions related to hypoxia. Animal models in vivo fail to recapitulate some of the key hallmarks of human physiology, which leads to human cell cultures; however, they are prone to bias, namely when pericellular oxygen concentration (partial pressure) does not respect oxygen dynamics in vivo. A search of the current literature on the topic revealed this was the case for many original studies pertaining to experimental models of hypoxia in vitro. Therefore, in this review, we present evidence mandating for the close control of oxygen levels in cell culture models of hypoxia. First, we discuss the basic physical laws required for understanding the oxygen dynamics in vitro, most notably the limited diffusion through a liquid medium that hampers the oxygenation of cells in conventional cultures. We then summarize up-to-date knowledge of techniques that help standardize the culture environment in a replicable fashion by increasing oxygen delivery to the cells and measuring pericellular levels. We also discuss how these tools may be applied to model both constant and intermittent hypoxia in a physiologically relevant manner, considering known values of partial pressure of tissue normoxia and hypoxia in vivo, compared to conventional cultures incubated at rigid oxygen pressure. Attention is given to the potential influence of three-dimensional tissue cultures and hypercapnia management on these models. Finally, we discuss the implications of these concepts for cell cultures, which try to emulate tissue normoxia, and conclude that the maintenance of precise oxygen levels is important in any cell culture setting.

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Section: Intermittent Hypoxiasupporting

confidence: 60%

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

Pavlacky

Polàk

2020

Front. Endocrinol.

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“…The focus of the present study was to investigate the functions of CCL2 and CCR2 in the 5-Aza-induced increase in THP-1 cell migration. CCR2 is an important marker of monocytic cells, and the binding of CCL2 to CCR2 results in the chemotaxis of monocytes (24,25). Therefore, the authors proposed that 5-Aza-induced THP-1 cell migration may be dependent on the CCL2-CCR2 axis.…”

Section: Discussionmentioning

confidence: 99%

“…The authors initially considered the possibility that 5-Aza may alter CCL2 and CCR2 expression via demethylating-dependent or independent mechanisms (26). The level of CCR2 expression is affected by stress, such as intermittent hypoxia (24). Therefore, the authors proposed that 5-Aza may influence the expression of CCL2 and CCR2 via a demethylation-independent mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Out of all inhibitors analyzed, only the ERK inhibitor was observed to prevent the 5-Aza-induced increase in THP-1 cell migration. In obstructive sleep apnea (OSA), intermittent hypoxia induces the activation of ERK1/2 and p38 MAPK signaling pathways in monocytic cells, and increases CCR2 expression and MCP-1-induced chemotaxis of monocytes (24). This indicates that the CCL2-CCR2 axis may promote the chemotaxis and adhesion of monocytes (24).…”

Section: Discussionmentioning

confidence: 99%

“…In obstructive sleep apnea (OSA), intermittent hypoxia induces the activation of ERK1/2 and p38 MAPK signaling pathways in monocytic cells, and increases CCR2 expression and MCP-1-induced chemotaxis of monocytes (24). This indicates that the CCL2-CCR2 axis may promote the chemotaxis and adhesion of monocytes (24). Yang et al (25) demonstrated that upregulation of CCL2 and CCR2 in low-metastatic nasopharyngeal carcinoma cell lines may promote cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

5-aza-2′-deoxycytidine promotes migration of acute monocytic leukemia cells via activation of CCL2-CCR2-ERK signaling pathway

Xiao

Sun

et al. 2017

Molecular Medicine Reports

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5-aza-2'-deoxycytidine (5-Aza) has been approved for clinical use in the treatment of myelodysplastic syndrome and acute myeloid leukemia (AML). It inhibits cell proliferation and induces cell differentiation by demethylating various genes, including tumor suppressor genes, transcription factors, and genes encoding cell cycle inhibitors. Although it has demonstrated efficacy in the clinic, drug resistance following 5-Aza treatment occurs. Cell migration and invasion following 5-Aza treatment are considered to be the key factors underlying drug resistance; however, there is currently limited information regarding the detailed mechanisms involved. In the present study, the THP-1 monocytic leukemia cell line was employed. The anti-leukemic functions of 5-Aza in THP-1 cells were first investigated. The results demonstrated that 5-Aza induced differentiation and inhibited THP-1 cell growth. Notably, 5-Aza significantly promoted THP-1 cell migration. Using reverse transcription-polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay analyses, 5-Aza treatment was observed to upregulate the expression of chemokine (C-C motif) ligand 2 (CCL2) and C-C chemokine receptor type 2 (CCR2) in THP-1 cells. In addition, the results demonstrated that CCL2 induced extracellular signal-regulated kinase (ERK) phosphorylation by CCR2 in 5-Aza-treated THP-1 cells. Treatment with a CCR2 or ERK inhibitor inhibited the 5-Aza-induced increase in THP-1 cell migration. In conclusion, the results of the present study provide an insight into the molecular mechanism underlying the 5-Aza-induced increase in THP-1 cell migration, as well as a potential strategy to overcome drug resistance in AML therapy.

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Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia

et al. 2015

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Increased C-C Chemokine Receptor 2 Gene Expression in Monocytes of Severe Obstructive Sleep Apnea Patients and under Intermittent Hypoxia

Cited by 16 publications

References 49 publications

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

5-aza-2′-deoxycytidine promotes migration of acute monocytic leukemia cells via activation of CCL2-CCR2-ERK signaling pathway

Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia

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