CCL2: A potential prognostic marker and target of anti‐inflammatory strategy in HIV/AIDS pathogenesis

Ansari, Abdul Wahid; Heiken, Hans; Meyer-Olson, Dirk; Schmidt, Reinhold

doi:10.1002/eji.201141676

Cited by 52 publications

(44 citation statements)

References 71 publications

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“…Several viruses induce MCP-1 expression upon infection and it has been shown that the chemokine promotes replication of human immunodeficiency virus (HIV) in macrophages4247. Here we showed for the first time that despite the apparent correlation between MCP-1 and CHIKV titre early in infection41736, this chemokine does not play a direct role in CHIKV replication.…”

Section: Discussionmentioning

confidence: 59%

Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Silva

Ende-Metselaar

Mulder

et al. 2016

Sci Rep

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Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection.

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Section: Discussionmentioning

confidence: 59%

Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Silva

Ende-Metselaar

Mulder

et al. 2016

Sci Rep

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“…In tumor-bearing mice, the CCR2-receptor is highly expressed by most MDSC subsets, and CCL2 alone is sufficient to induce migration of MDSCs [39]. It has been shown that CCL2 is up-regulated upon HIV infection [40]. Based on this, we proposed that changes in CCL2 levels might be responsible for the trafficking of the MDSCs from BM to the periphery in the SIV-infected macaques.…”

Section: Resultsmentioning

confidence: 96%

Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV chronically infected macaques

et al. 2017

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Myeloid derived suppressor cells (MDSCs), which suppress anti-tumor or anti-viral immune responses, are expanded in the peripheral blood and tissues of patients/animals with cancer or viral infectious diseases. We here show that in chronic SIV infection of Indian rhesus macaques, the frequency of MDSCs in the bone marrow (BM) was paradoxically and unexpectedly decreased, but increased in peripheral blood. Reduction of BM MDSCs was found in both CD14+MDSC and Lin-CD15+MDSC subsets. The reduction of MDSCs correlated with high plasma viral loads and low CD4+ T cell counts, suggesting that depletion of BM MDSCs was associated with SIV/AIDS disease progression. Of note, in SHIVSF162P4-infected macaques, which naturally control viral replication within a few months of infection, the frequency of MDSCs in the bone marrow was unchanged. To investigate the mechanisms by which BM MDSCs were reduced during chronic SIV infection, we tested several hypotheses: depletion due to viral infection, alterations in MDSC trafficking, and/or poor MDSC replenishment. We found that the possible mobilization of MDSCs from BM to peripheral tissues and the slow self-replenishment of MDSCs in the BM, along with the viral infection-induced depletion, all contribute to the observed BM MDSC reduction. We first demonstrate MDSC SIV infection in vivo. Correlation between BM CD14+MDSC reduction and CD8+ T cell activation in tissues is consistent with decreased immune suppression by MDSCs. Thus, depletion of BM MDSCs may contribute to the pathologic immune activation during chronic SIV infection and by extension HIV infection.

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“…Physiologically, chemokines are expressed to recruit and direct cell trafficking/migration (32). They control the movement of certain transmembrane G protein-coupled receptor (GPCR)-expressing cells.…”

Section: Factor Analysis Identified Cinc1-3 Mip-1/3` Mig Rantes Anmentioning

confidence: 99%

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

Abdel-Aziz

Schneider

Neuhuber

et al. 2015

Mol Med

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Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein-coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1-3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1-3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.

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CCL2: A potential prognostic marker and target of anti‐inflammatory strategy in HIV/AIDS pathogenesis

Cited by 52 publications

References 71 publications

Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV chronically infected macaques

GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

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