The Role of Oxidative Stress in Sarcoidosis

Fois, Sara S.; Canu, Sara; Fois, Alessandro Giuseppe

doi:10.3390/ijms222111712

Cited by 5 publications

(4 citation statements)

References 109 publications

(114 reference statements)

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“…In sarcoidosis, the production of ROS is enhanced and is thought to contribute to tissue destruction around the granulomas ( 24 ). The production of ROS primarily occurs in giant cells; ( 7 , 8 ) however, this study has also demonstrated an enhancement of ROS in TREM2_2 macrophages.…”

Section: Resultsmentioning

confidence: 99%

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

Nakamizo,

Sugiura,

Ishida

et al. 2023

Journal of Clinical Investigation

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Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2–positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1,6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis.

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Section: Resultsmentioning

confidence: 99%

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

Nakamizo,

Sugiura,

Ishida

et al. 2023

Journal of Clinical Investigation

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“…Sarcoidosis, a highly prevalent granulomatous disease of unknown cause [19] , is usually common in the lungs but can affect almost all organs [20] . Lipid molecules are involved in triggering and resolving in ammation in lung diseases, and abnormal lipid metabolic pathways are involved in the pathogenesis of many lung diseases [21] .…”

Section: Discussionmentioning

confidence: 99%

Genetic association of lipids and lipid-lowering drug target genes with sarcoidosis

Tan,

Liang,

Liu

et al. 2024

Preprint

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Objective: Todetermine the potential causal association between serum lipid levels and sarcoidosis, and to investigate the potential impact of lipid-lowering agents on sarcoidosis. Methods: Two-sample Mendelian randomization (TSMR) was used to investigate the association between lipid levels (including LDL-c, HDL-c, TG, and TC) and sarcoidosis risk. In addition, we conducted a comprehensive analysis of the relationship between lipid-lowering drugs and sarcoidosis, utilizing Mendelian randomization of drug targets (DMR). Results: According to the TSMR analysis, a positive correlation was observed between the serum LDL-c concentration and sarcoidosis incidence (n = 153 SNPs, OR = 1.232, 95% CI = 0.990 - 1.732; p = 0.031). Similarly, serum TG concentration was found to be positively associated with sarcoidosis (n = 52 SNPs, OR = 1.287, 95% CI = 1.024 - 1.617; p = 0.03). The DMR results demonstrated a positive correlation between PCSK9-mediated serum LDL-c levels and sarcoidosis (n = 35 SNPs, OR = 1.681, 95% CI = 1.220 - 2.315; p = 0.001). Similarly, serum TG levels mediated by LPL were positively associated with sarcoidosis (n = 28 SNPs, OR = 1.569, 95% CI = 1.223 - 2.012; p = 3.93E-04). Conclusions: This study suggested that elevated serum TG and LDL-c levels may increase the risk of sarcoidosis. The use of PCSK9 inhibitors and LPL-type lipid-lowering drugs is expected to increase the risk of sarcoidosis.

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“…72 However, conditions of chronic inflammation result in an overwhelming production of reactive oxygen species and reactive nitrogen species, at the expense of the antioxidant defense system leading to oxidative stress. 73,74 In ILD, reactive oxygen species plays a role in fibrosis and tissue damage. 75 There is considerable evidence that antioxidants play a key role in diminishing inflammation in patients with chronic lung disease.…”

Section: Antioxidants and Other Inflammatory Mediatorsmentioning

confidence: 99%

“…Under normal conditions, these free radicals, reactive oxygen species, and reactive nitrogen species are then efficiently scavenged by the antioxidant defense system including vitamins and enzymes such as carotenoids, vitamins C and E, selenium and glutathione 72 . However, conditions of chronic inflammation result in an overwhelming production of reactive oxygen species and reactive nitrogen species, at the expense of the antioxidant defense system leading to oxidative stress 73,74 …”

Section: Micronutrientsmentioning

confidence: 99%

Nutrition implications of intrinsic restrictive lung disease

et al. 2022

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Restrictive lung disease is defined as a reduction in lung volume that may be due to intraparenchymal or extraparenchymal causes. Intraparenchymal causes falls under the umbrella term of interstitial lung disease (ILD) and includes idiopathic pulmonary fibrosis. This manuscript provides an overview of ILD and can be beneficial for all clinicians working with patients with ILD. Although not well documented, the prevalence of malnutrition in patients with ILD has been reported to be between ~9% and 55%. Body mass index has been shown to predict survival; but more recently, research has suggested that fat‐free mass has a larger influence on survival. There is insufficient evidence to support the use of antioxidant or vitamin supplementation to help diminish the chronic inflammatory process that is seen in this patient population. There are data from studies examining the vitamin D status in this patient population, but research on vitamin D supplementation appears to be lacking. Registered dietitian nutritionists should continue to advocate and play a more prominent role in the nutrition management of patients with ILD as part of standard of care.

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The Role of Oxidative Stress in Sarcoidosis

Cited by 5 publications

References 109 publications

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

Genetic association of lipids and lipid-lowering drug target genes with sarcoidosis

Nutrition implications of intrinsic restrictive lung disease

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