Tissue-Resident Alveolar Macrophages Do Not Rely on Glycolysis for LPS-induced Inflammation

Woods, P.S.; Kimmig, Lucas; Meliton, Angelo Y.; Sun, K.; Tian, Yufeng; O’Leary, Erin; Gökalp, G.; Hamanaka, Robert B.; Mutlu, Gökhan M.

doi:10.1165/rcmb.2019-0244oc

Cited by 98 publications

(92 citation statements)

References 47 publications

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“…Lungs are the primary site of entry for PM, and we have previously demonstrated that alveolar macrophages (AMs) are metabolically distinct from BMDMs (Woods, Kimmig et al 2020). We thus sought to determine whether the role of itaconate in AMs is similar to what we observed in BMDMs.…”

Section: Itaconate Does Not Modulate Pm-induced Inflammation or Nrf2 mentioning

confidence: 99%

“…All animal experiments and procedures were performed according to the protocols approved by the Institutional Animal Care and Use Committee at the University of Chicago. We used primary murine cells (bone marrow-derived macrophages (BMDMs)), which we isolated as we have recently reported (Woods, Kimmig et al 2020 qRT-PCR primer sequences used are as follows:…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…The Seahorse XF e 24 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA), was used to measure oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) as we have previously described (Nigdelioglu, Hamanaka et al 2016, Hamanaka, O'Leary et al 2019, Soberanes, Misharin et al 2019, Woods, Kimmig et al 2020).…”

Section: Seahorse Analysismentioning

confidence: 99%

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Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Sun

Meliton

et al. 2020

eLife

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Particulate matter (PM) air pollution causes cardiopulmonary mortality via macrophage-driven lung inflammation; however, the mechanisms are incompletely understood. RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by PM in macrophages. Acod1 encodes a mitochondrial enzyme that produces itaconate, which has been shown to exert anti-inflammatory effects via NRF2 after LPS. Here, we demonstrate that PM induces Acod1 and itaconate, which reduced mitochondrial respiration via complex II inhibition. Using Acod1-/- mice, we found that Acod1/endogenous itaconate does not affect PM-induced inflammation or NRF2 activation in macrophages in vitro or in vivo. In contrast, exogenous cell permeable itaconate, 4-octyl itaconate (OI) attenuated PM-induced inflammation in macrophages. OI was sufficient to activate NRF2 in macrophages; however, NRF2 was not required for the anti-inflammatory effects of OI. We conclude that the effects of itaconate production on inflammation are stimulus-dependent, and that there are important differences between endogenous and exogenously-applied itaconate.

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Section: Itaconate Does Not Modulate Pm-induced Inflammation or Nrf2 mentioning

confidence: 99%

Section: Cell Isolation and Culturementioning

confidence: 99%

Section: Seahorse Analysismentioning

confidence: 99%

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Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Sun

Meliton

et al. 2020

eLife

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“…All animal experiments and procedures were performed according to the protocols approved by the Institutional Animal Care and Use Committee at the University of Chicago. We used primary murine cells (bone marrow-derived macrophages (BMDMs), which we isolated as we have recently reported (Woods, Kimmig et al 2019). Hematopoietic cells were isolated from bone marrow of C57BL/6NJ (Stock No: 005304) and Acod1 -/- (…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…The Seahorse XF e 24 Extracellular Flux Analyzer (Seahorse Bioscience, North Billerica, MA), was used to measure oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) as we have previously described (Nigdelioglu, Hamanaka et al 2016, Soberanes, Misharin et al 2019, Woods, Kimmig et al 2019). Macrophages were seeded at a density of 4  10 4 per well on a Seahorse XF24 Cell Culture Microplate (Woods, Kimmig et al 2019).…”

Section: Seahorse Analysismentioning

confidence: 99%

Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Sun

Meliton

et al. 2020

Preprint

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ABSTRACTParticulate matter (PM) air pollution causing significant cardiopulmonary mortality via macrophage-driven lung inflammation; however, the mechanisms are not completely understood. RNA-sequencing demonstrated Acod1 (Aconitate decarboxylase 1) as one of the top genes induced by PM in macrophages. Acod1 encodes a mitochondrial enzyme that produces itaconate, which has been shown to exert anti-inflammatory effects via NRF2 after LPS. Here, we demonstrate that PM induces Acod1 and itaconate, which reduced mitochondrial respiration via complex II inhibition. Using Acod1-/- macrophages, we found that Acod1/endogenous itaconate was not required for PM-induced inflammation or NRF2 activation. In contrast to endogenous itaconate, exogenous cell permeable form of itaconate (4-octyl itaconate (OI)) attenuated the PM-induced inflammation and activated NRF2 but NRF2 was not required for the anti-inflammatory effects of OI. We conclude that the effects of itaconate production on inflammation are stimulus-dependent, and that there are important differences between endogenous and exogenously-applied itaconate.

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Lung Immune Cell Niches and the Discovery of New Cell Subtypes

Shan,

Qiu,

Dong

et al. 2024

Advanced Science

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Immune cells in the lungs are important for maintaining lung function. The importance of immune cells in defending against lung diseases and infections is increasingly recognized. However, a primary knowledge gaps in current studies of lung immune cells is the understanding of their subtypes and functional heterogeneity. Increasing evidence supports the existence of novel immune cell subtypes that engage in the complex crosstalk between lung‐resident immune cells, recruited immune cells, and epithelial cells. Therefore, further studies on how immune cells respond to perturbations in the pulmonary microenvironment are warranted. This review explores the processes behind the formation of the immune cell niche during lung development, and the characteristics and cell interaction modes of several major lung‐resident immune cells. It indicates that distinct lung microenvironments or inflammatory niches can mediate the formation of different cell subtypes. These findings summarize and clarify paths to identify new cell subtypes that originate from resident progenitor cells and recruited peripheral cells, which are remodeled by the pulmonary microenvironment. The development of new techniques combining transcriptome analysis and location information is essential for identifying new immune cell subtypes and their relative immune niches, as well as for uncovering the molecular mechanisms of immune cell‐mediated lung homeostasis.

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Tissue-Resident Alveolar Macrophages Do Not Rely on Glycolysis for LPS-induced Inflammation

Cited by 98 publications

References 47 publications

Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Endogenous itaconate is not required for particulate matter-induced NRF2 expression or inflammatory response

Lung Immune Cell Niches and the Discovery of New Cell Subtypes

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