Coordinated Post-Transcriptional Regulation of the Chemokine System: Messages from CCL2

Panganiban, Ronaldo Paolo; Vonakis, Becky M.; Ishmael, Faoud T.; Stellato, Cristiana

doi:10.1089/jir.2013.0149

Cited by 27 publications

(23 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 19 , 20 Involvement of CCL2 in macrophage and mast cell recruitment in the lung is supported by several experimental mouse models of inflammation and emphysema, constituting an attractive therapeutic target. 20 Although well known to be regulated posttranscriptionally in airway epithelium by TTP and HuR, 60 association of CCL2 mRNA with AUF-1 has not been yet fully characterized; similarly, direct association of AUF-1 with other epithelial genes relevant to COPD pathogenesis overexpressed upon cytomix treatment, such as CCL5, CXCL10, and CXCL11, remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of RNA-binding proteins in bronchial epithelium of stable COPD patients

Ricciardi¹,

Col²,

Casolari³

et al. 2018

COPD

Self Cite

View full text Add to dashboard Cite

PurposeInflammatory gene expression is modulated by posttranscriptional regulation via RNA-binding proteins (RBPs), which regulate mRNA turnover and translation by binding to conserved mRNA sequences. Their role in COPD is only partially defined. This study evaluated RBPs tristetraprolin (TTP), human antigen R (HuR), and AU-rich element-binding factor 1 (AUF-1) expression using lung tissue from COPD patients and control subjects and probed their function in epithelial responses in vitro.Patients and methodsRBPs were detected by immunohistochemistry in bronchial and peripheral lung samples from mild-to-moderate stable COPD patients and age/smoking history-matched controls; RBPs and RBP-regulated genes were evaluated by Western blot, ELISA, protein array, and real-time PCR in human airway epithelial BEAS-2B cell line stimulated with hydrogen peroxide, cytokine combination (cytomix), cigarette smoke extract (CSE), and following siRNA-mediated silencing. Results were verified in a microarray database from bronchial brushings of COPD patients and controls. RBP transcripts were measured in peripheral blood mononuclear cell samples from additional stable COPD patients and controls.ResultsSpecific, primarily nuclear immunostaining for the RBPs was detected in structural and inflammatory cells in bronchial and lung tissues. Immunostaining for AUF-1, but not TTP or HuR, was significantly decreased in bronchial epithelium of COPD samples vs controls. In BEAS-2B cells, cytomix and CSE stimulation reproduced the RBP pattern while increasing expression of AUF-1-regulated genes, interleukin-6, CCL2, CXCL1, and CXCL8. Silencing expression of AUF-1 reproduced, but not enhanced, target upregulation induced by cytomix compared to controls. Analysis of bronchial brushing-derived transcriptomic confirmed the selective decrease of AUF-1 in COPD vs controls and revealed significant changes in AUF-1-regulated genes by genome ontology.ConclusionDownregulated AUF-1 may be pathogenic in stable COPD by altering posttranscriptional control of epithelial gene expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential expression of RNA-binding proteins in bronchial epithelium of stable COPD patients

Ricciardi¹,

Col²,

Casolari³

et al. 2018

COPD

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because CCL2 plays a neuroprotective role during an ischemic preconditioning and postconditioning process [ 5 , 40 , 41 ], zinc finger transcription factor ZXDC might mediate CCL2-induced neuroprotection. Moreover, several references support the upregulation of CCL2 through HuR proteins, miRNAs, and inflammatory cytokines (IL-17 and TNF α ), which promote stability of CCL2 mRNA after their binding to ARE's regions [ 59 – 61 ]. These mechanisms might also mediate CCL2-induced neuroprotection administered when zinc is administered prior to the ischemic event.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

et al. 2015

View full text Add to dashboard Cite

Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

show abstract

“…MCP1 or CCL2 regulates the migration and infiltration of cells expressing the receptor CCR2, which includes monocytes, memory T lymphocytes, and NK cells, and is produced either constitutively or after induction by oxidative stress or pro-inflammatory mediators. It also participates in the phenotypic polarization of memory T cells toward a Th2 phenotype ( 165 , 166 ). MCP1 is produced by several different cell types, including endothelial, fibroblast, epithelial, smooth muscle, and monocyte cells among others, monocyte and macrophages being the main sources ( 167 ).…”

Section: Cytokines and Chemokines With Increased Expression During Sementioning

confidence: 99%

Modulating the Innate Immune Response to Influenza A Virus: Potential Therapeutic Use of Anti-Inflammatory Drugs

2015

View full text Add to dashboard Cite

Infection by influenza A viruses (IAV) is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV are consequences of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models in reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e., NF kappa B transcription factors) and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.

show abstract

Coordinated Post-Transcriptional Regulation of the Chemokine System: Messages from CCL2

Cited by 27 publications

References 101 publications

Differential expression of RNA-binding proteins in bronchial epithelium of stable COPD patients

Differential expression of RNA-binding proteins in bronchial epithelium of stable COPD patients

Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

Modulating the Innate Immune Response to Influenza A Virus: Potential Therapeutic Use of Anti-Inflammatory Drugs

Contact Info

Product

Resources

About