A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

Collins, Morgan K.; Shotland, Abigail M.; Wade, Morgan F.; Atif, Shaikh M.; Richards, Denay; Torres-Llompart, Manolo; Mack, Douglas G.; Martin, Allison K.; Fontenot, Andrew P.; McKee, Amy S.

doi:10.1172/jci.insight.134356

Cited by 14 publications

(7 citation statements)

References 77 publications

(138 reference statements)

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“…We found that transplanting WT BM into our lincRNA-Cox2 mutant mice completely rescued the neutrophil and cytokine/chemokine phenotype in the BAL (Figure 7B-K). While we aimed to determine if lincRNA-Cox2 functions either through resident (SiglecF+) or recruited (Siglec F-) alveolar macrophages, we found that both populations were composed of >70% donor BM (SFigure 8I-J) indicating that radiation obliterated resident SiglecF+ alveolar cells which become repopulated with donor cells from the bone marrow (Guilliams et al , 2013; Hashimoto et al , 2013; Misharin et al , 2017; Collins et al , 2020; Gangwar et al , 2020). These experiments enable us to conclude that lincRNA-Cox2 expression originating from the bone marrow can function to control immune responses in the lung, since BM derived immune cells transplanted into lincRNA-Cox2 mutant mice are able to rescue the phenotype driven by loss of lincRNA-Cox2 in the lung.…”

Section: Discussionmentioning

confidence: 99%

LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

Robinson

Worthington

Poscablo

et al. 2021

Preprint

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The respiratory system exists at the interface between our body and the surrounding non-sterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of pro- and anti- inflammatory cues. An appropriate inflammatory response is vital for combating pathogens, while an excessive or uncontrolled inflammatory response can lead to the development of chronic diseases. Recent studies show that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. LincRNA-Cox2 is one such example of an inflammatory inducible long noncoding RNA functioning to control immune response genes. Here using bulk and single cell RNA-seq, in addition to florescence activated cell sorting, we show that lincRNA-Cox2 is most highly expressed in the lung, particularly in alveolar macrophages where it functions to control immune gene expression following acute lung injury. Utilizing a newly generated lincRNA-Cox2 transgenic overexpressing mouse, we show that it can function in trans to control genes including Ccl3, 4 and 5. This work greatly expands our understanding of the role for lincRNA-Cox2 in host defense and sets in place a new layer of regulation in RNA-immune-regulation of genes within the lung.

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Section: Discussionmentioning

confidence: 99%

LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

Robinson

Worthington

Poscablo

et al. 2021

Preprint

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“…In a following study, the authors showed that beryllium induced tumor necrosis factor-α (TNF)-α production by alveolar macrophages which enhanced the release of DNA and boost intercellular levels of interleukin-1α (IL-1α) which is released upon cell death. Using a CBD mouse model, it was shown that blockage of TNF-α prevented the expansion of beryllium effector T-cells in the lung draining lymph nodes after beryllium challenge and that the number and size of lymphocyte infiltrates in the lungs were decreased compared to mice not treated with anti-TNF-α [51 ▪ ]. Those results suggest that TNF-α antibodies may be an effective treatment option for patients with CBD.…”

Section: Lessons Learned From Chronic Beryllium Disease and Silicosismentioning

confidence: 92%

“…It is not known whether the results of Collins et al regarding TNF-α in CBD can be attributed to other inorganic agents. They however observed that aluminum enhanced the release of TNF-α by alveolar macrophages in a similar extent as beryllium [51 ▪ ] and also silica was found to stimulate TNF-α production by macrophages [53 ▪ ]. Furthermore, both aluminum and silica have been found to cause alveolar cell death and release of IL-1α and DNA [54].…”

Section: Lessons Learned From Chronic Beryllium Disease and Silicosismentioning

confidence: 96%

The emerging role of inorganic elements as potential antigens in sarcoidosis

Beijer

Veltkamp

2021

Current Opinion in Pulmonary Medicine

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Purpose of reviewPrevious studies mainly described a role for organic agents as possible triggers for sarcoidosis. In this review, we address recent studies suggesting a possible role for inorganic elements, such as metals or silica in sarcoidosis pathogenesis.Recent findingsSeveral epidemiological papers suggest that inorganic agents, either by environmental exposures or occupational activities, could trigger sarcoidosis. Association between inorganics and sarcoidosis is also described in several recently published case reports and studies demonstrating immunological sensitization to inorganic agents in sarcoidosis patients.Studies comparing chronic beryllium disease (CBD) and sarcoidosis suggest that although antigenic triggers may differ, underlying processes may be comparable.Besides the fact that a growing number of studies show a possible role for inorganic triggers, it is also suggested that inorganic triggered sarcoidosis may result in a more severe phenotype, including pulmonary fibrosis.SummaryWe can use the knowledge already gained on CBD pathogenesis to conduct further research into role of inorganics, such as metals and silica as antigens in sarcoidosis. Given the importance of a lymphocyte proliferation test (LPT) in diagnosing CBD, it seems obvious to also implement this test in the diagnostic work-up of sarcoidosis to identify patients with an inorganic antigenic trigger of their disease.

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“…TNF-α is an important pro-inflammatory cytokine and during malaria has been correlated with the development of anemia [36]. The anemia in these patients may thus be developed as a result of the inflammatory response of these cytokines and the generation of a damage-associated molecular pattern (DAMPs) [37,38] and/or due to a strong TH2 response that favors the persistence of the parasite and is generated by the natural cycle of Plasmodium replication that leads to red blood cells lysis.…”

Section: Plos Onementioning

confidence: 99%

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection

et al. 2022

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Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

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A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

Cited by 14 publications

References 77 publications

LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

The emerging role of inorganic elements as potential antigens in sarcoidosis

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection

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