Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling

Yang, Lifeng; Tang, Lian; Le, Yulan; Yao, Wenjuan

doi:10.2131/jts.42.763

Cited by 41 publications

(38 citation statements)

References 30 publications

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“…Also, we found that asthmatic lung tissues showed activated RhoA signaling, and inhibition of RhoA signaling prevented CRE-induced airway inflammation and remodeling in a chronic mouse model of asthma (30). Furthermore, the activation of RhoA signaling has been associated with macrophage polarization (62,63). In this study, we provided evidence that Ccl2 can activate RhoA signaling, and that inhibition of RhoA signaling can block Ccl2-induced M1 macrophage polarization.…”

Section: Discussionmentioning

confidence: 53%

“…Thus, the insufficient amount of Ccl2 caused by miR-511-3p fails to polarize macrophages into an inflammatory M1 phenotype, thereby leading to the reduction of allergic inflammation. ferentiation induced by PMA (19,39). Furthermore, we have previously demonstrated that Ptgds (encoding hematopoietic prostaglandin D synthase), which catalyzes the conversion of PGH2 to PGD2, may be one of the direct target genes for miR-511-3p (10).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

Danh¹,

Mu²,

Xia³

et al. 2019

JCI Insight

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

Danh¹,

Mu²,

Xia³

et al. 2019

JCI Insight

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“…This is of vital importance as cellular signaling is largely governed by the regulation of expression of kinases and phosphatases in a cell type-specific manner or upon cell activation (51-53). One of the major findings of this study is the differential expression of key regulatory kinases implicated in cell cycle regulation including cyclin-dependent kinases, NEK family of serine-threonine kinases as well as cAMP/PKA-induced signaling that are collectively responsible for enrichment of signaling pathways involved in differentiation, maturation, and regulation of actin cytoskeleton dynamics (54, 55). Interestingly, a pronounced decrease in the expression of vital regulatory kinases in cell cycle entry and checkpoint including the cyclin-dependent kinases has been reported in a previous study exploring the role of kinases in monocyte-macrophage differentiation (22).…”

Section: Discussionmentioning

confidence: 99%

Dose-dependent phorbol 12-myristate-13-acetate-mediated monocyte-to-macrophage differentiation induces unique proteomic signatures in THP-1 cells

Pinto

Kim

Subbannayya

et al. 2020

Preprint

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1, 2). Monocytes in the blood circulation migrate to the site of infection/inflammation and 48 differentiate into macrophages for effective host defense, tissue remodeling, and repair (3). 49Furthermore, macrophages exhibit a high level of plasticity, depending on their local 50 microenvironment, specialized functions and varied phenotype acquired (1, 4). 51Several models are employed to study the mechanisms of immune-modulation in monocytes 52 and macrophages during inflammatory diseases. The most frequently used include primary 53 peripheral blood mononuclear cells (PBMCs) and monocyte cell lines. However, due to donor-54 to-donor variations and technical disparities involved in handling of PBMCs in vitro, the 55 human leukemia monocytic cell line, THP-1, is widely accepted and used as a 56 monocyte/macrophage model (5, 6). Several studies have indicated that THP-1 cells can be 57 differentiated into macrophage-like cells using phorbol-12-myristate-13-acetate (PMA), 58 which markedly resembles PBMC monocyte-derived macrophages (MDMs) in cytokine 59 production, metabolic and morphological properties, including differential expression of 60 macrophage surface markers such as CD14, CD11b (ITGAM) and scavenger receptors-CD163, 61 MSR1, and SCARB2 (5, 7-10). Nonetheless, depending on the parameters of the differentiation 62 protocol employed, such as the concentration (ranging from 5 to 400 ng/mL), and duration of 63 incubation (1 to 5 days) with PMA; the degree of differentiation and the functional changes 64 may vary significantly (5,(11)(12)(13)(14)(15). 65At the molecular level, multiple proteins including growth factors, antigenic markers, 66 chemokine-receptors, cytokines, and cell adhesion molecules, are known to govern and reflect 67 underlying monocyte-macrophage differentiation processes (16)(17)(18)(19)(20). However, the effect of 68 various differentiation protocols on the cellular proteome and intracellular signaling networks 69 4 during monocyte-to-macrophage differentiation remains poorly understood. Hence, it is crucial 70 to determine the most suitable differentiation conditions when using these cells as model 71 system, as this can significantly impact their response to various innate immune stimuli. 72Quantitative high-resolution mass spectrometry-based proteomic approaches have been widely 73 employed to investigate the proteomes of monocytes and macrophages as well as altered 74 cellular proteomes and complex cellular/biological mechanisms in several biological 75 conditions (21-23). However, to date, no studies have directly compared the proteome changes 76 of the PMA-mediated differentiation process. 77In the present study, we evaluate the effect of three PMA-based differentiation protocols on 78 the changes in the proteome profiles upon THP-1 differentiation using stable isotope dimethyl 79 labeling quantitative proteomics. We demonstrate that various differentiation conditions such 80 as concentration and incubation time, prior to any stimuli, are critical consideration factors for 81 hetero...

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“…RhoGTP enzyme family members, including Rho, Rac and Cdc42, are closely associated with cytoskeleton reorganization and serve an important role in cell motility, migration and invasion (34). The degree of Rac signaling plays a crucial role in the balance between differentiation and proliferation; cellular Rac1 is indispensable for differentiation (35), and RhoA/ROCK signaling plays an important role in differentiation induction (36). The activation of Rho and Rac1 can phosphorylate the kinase ROCK and activate LIMK1, as Rac can activate LIMK1, which induces cofilin 1 phosphorylation at Ser3 and thus regulates the actin cytoskeleton; this process indicates the formation of the Rac1-ROCK1/LIMK1-cofilin signaling pathway by regulating tumor cell migration and invasion (37,38).…”

Section: Groupmentioning

confidence: 99%

Diallyl disulfide induces downregulation and inactivation of cofilin�1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells

Ling

Lei

et al. 2020

Int J Oncol

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Cofilin is associated with cell differentiation; however, to the best of our knowledge, no data have indicated an association between the cofilin 1 pathway and leukemia cell differentiation. The present study investigated the involvement of the cofilin 1 signaling pathway in diallyl disulfide (DADS)-induced differentiation and the inhibitory effects on the proliferation, migration, and invasion of human leukemia HL-60 cells. First, it was identified that 8 µM DADS suppressed cell proliferation, migration and invasion, and induced differentiation based on the reduced nitroblue tetrazolium ability and increased CD11b and CD33 expression. DADS significantly downregulated the expression of cofilin 1 and phosphorylated cofilin 1 in HL-60 leukemia cells. Second, it was verified that silencing cofilin 1 markedly promoted 8 µM DADS-induced differentiation and the inhibitory effect on cell proliferation and invasion. Overexpression of cofilin 1 obviously suppressed 8 µM DADS-induced differentiation and the inhibitory effect on cell proliferation and invasion. Third, the present study examined the mechanisms by which 8 µM DADS decreases cofilin 1 expression and activation. The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho-associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL-60 cells, while 8 µM DADS enhanced the effects of the Rac1-ROCK1-LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL-60 cells. These results suggest that the anticancer function of DADS on HL-60 leukemia cells is regulated by the Rac1-ROCK1-LIMK1-cofilin 1 pathway, indicating that DADS could be a promising anti-leukemia therapeutic compound.

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Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling

Cited by 41 publications

References 30 publications

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

miR-511-3p protects against cockroach allergen–induced lung inflammation by antagonizing CCL2

Dose-dependent phorbol 12-myristate-13-acetate-mediated monocyte-to-macrophage differentiation induces unique proteomic signatures in THP-1 cells

Diallyl disulfide induces downregulation and inactivation of cofilin�1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells

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