MAPping the kinase landscape of macrophage activation

Platko, Khrystyna; Lebeau, Paul; Austin, Richard C.

doi:10.1074/jbc.h118.003380

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…As a first step in elucidating WTC dust-induced SGD mechanisms, we analyzed the expression of markers of oxidative stress, inflammation, and injury in lung and/or lymph nodes of WTC dust-exposed patients followed in our clinic. Lung and/or lymph node samples from all patients examined stained positively for markers of pro-inflammatory M1 macrophages including iNOS, COX-2, TNFα and ARL11 [ 21 , 22 , 23 ]. iNOS and COX-2 mediate the production of reactive nitrogen species and proinflammatory eicosanoids, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, COX-2 has been reported to be upregulated by silica, a component of WTC dust, in rodents, cultured fibroblasts, and in sarcoid granulomas [ 4 , 18 , 24 , 25 , 26 ]. ARL11 has recently been identified as a regulator of proinflammatory macrophage activation and TNFα release [ 22 , 27 ]. TNFα has been implicated in lung injury induced by silica [ 26 ], suggesting a potential mechanism of disease pathogenesis following WTC dust exposure.…”

Section: Discussionmentioning

confidence: 99%

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Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers

Sunil

Radbel

Hussain

et al. 2019

IJERPH

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Sarcoid-like granulomatous diseases (SGD) have been previously identified in cohorts of World Trade Center (WTC) dust-exposed individuals. In the present studies, we analyzed lung and/or lymph node biopsies from patients referred to our clinic with suspected WTC dust-induced lung disease to evaluate potential pathophysiologic mechanisms. Histologic sections of lung and/or lymph node samples were analyzed for markers of injury, oxidative stress, inflammation, fibrosis, and epigenetic modifications. Out of seven patients examined, we diagnosed four with SGD and two with pulmonary fibrosis; one was diagnosed later with SGD at another medical facility. Patients with SGD were predominantly white, obese men, who were less than 50 years old and never smoked. Cytochrome b5, cytokeratin 17, heme oxygenase-1, lipocalin-2, inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, ADP-ribosylation factor-like GTPase 11, mannose receptor-1, galectin-3, transforming growth factor β, histone-3 and methylated histone-3 were identified in lung and lymph nodes at varying levels in all samples examined. Three of the biopsy samples with granulomas displayed peri-granulomatous fibrosis. These findings are important and suggest the potential of WTC dust-induced fibrotic sarcoid. It is likely that patient demographics and/or genetic factors influence the response to WTC dust injury and that these contribute to different pathological outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers

Sunil

Radbel

Hussain

et al. 2019

IJERPH

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“…The mechanism described proposes that Arl11 interacts and colocalizes with ERK1/2 (MAPK downstream of Toll-like receptor 4 (TLR4) signaling) on the actin cytoskeleton and promotes ERK1/2 phosphorylation, which is required for pro-inflammatory cytokine production upon LPS/ pathogen stimuli. Further, ectopic expression of Arl11 led to prolonged activation of the ERK1/2 pathway, leading to upregulation of the apoptotic machinery (Arya et al, 2018;Platko et al, 2018). This study is the first to report on the cellular function of Arl11.…”

Section: Arl11mentioning

confidence: 71%

Emerging roles of Arl GTPases in regulating cellular functions

Sharma

Marwaha

Dwivedi

2019

PINSA

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Members of Rab and ADP-ribosylation factor (Arf) family of small GTP-binding (G) proteins regulate several aspects of intracellular transport and cytoskeleton organization. The phylogenetic analysis, combined with database mining approaches has led to the identification of Arf-like (Arl) G proteins as a sub-group of the Arf family with approximately 20 members in mammals. Arls are similar in structure to the Arfs, but exhibit immense diversity pertaining to their mechanisms of membrane recruitment, subcellular distribution and cellular functions. Only a few members of this sub-group are currently characterized, while information on the majority of Arl proteins remains scanty or is not known. In this review, we will cover our current understanding of the functions performed by Arl sub-family members, described under three broad categories: Arls involved in primary cilia formation and function, Arls engaged in secretory and endocytic transport, and Arls regulating microtubule and actin organization.

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“…Upon encounter of gram-negative bacteria by macrophages, LPS present on either the surface of a bacterium or shed by bacteria in the blood flow is captured by LBP (LPS-binding protein) and presented as a ligand to TLR4, a type I transmembrane protein present on the plasma membrane of macrophage that mediate the recognition of PAMPS such as LPS (Shimazu et al, 1999). The engagement of LPS with TLR4 (along with other co-stimulatory molecules) leads to recruitment of several adaptor proteins at the cytoplasmic tail of TLR4 followed by a cascade of intracellular events leading to activation of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling cascades downstream to TLR4 including ERK1/2 (Buscher et al, 1995; Schaeffer and Weber, 1999; Gay et al, 2014; Platko et al, 2018; Arya et al, 2018). These signaling pathways directly or indirectly phosphorylate and activate various transcription factors that lead to the expression of genes involved in production and release of pro-inflammatory cytokines, reactive oxygen species, nitrosative burst and promotes macrophage activation (Satoh and Akira, 2016).…”

Section: Introductionmentioning

confidence: 99%

Method for Studying the Effect of Gene Silencing on Bacterial Infection-induced ERK1/2 Signaling in Bone-marrow Derived Macrophages

2018

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Macrophages are highly phagocytic cells that utilize various pathogen recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs). These PAMPs can be present within the microbe, such as bacterial CpG DNA, and are recognized by Toll-like receptor 9 (TLR9), a PRR present on the endosomal membrane of macrophages. PAMPs can also be present on the surface of microbes, such as Lipopolysaccharide (LPS), which decorates the outer membrane of gram-negative bacteria like Salmonella typhimurium and Escherichia coli. LPS is recognized by TLR4 present on the plasma membrane of macrophages, and LPS-TLR4 association leads to activation of signaling cascades including MAPK phosphorylation, which in turn promotes macrophage activation and microbial killing. This protocol describes the method for studying the role of a gene of interest in Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signaling, induced by bacterial infection in primary bone-marrow derived macrophages (BMDMs).

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MAPping the kinase landscape of macrophage activation

Cited by 4 publications

References 7 publications

Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers

Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers

Emerging roles of Arl GTPases in regulating cellular functions

Method for Studying the Effect of Gene Silencing on Bacterial Infection-induced ERK1/2 Signaling in Bone-marrow Derived Macrophages

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