Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment

Morsi, Ahmed; Faruk, Eman Mohamed; Mogahed, Mysara Mohamed; Baioumy, Bodour; Hussein, Asmaa Y. A.; EL-Shafey, Rabab Shaban; Mersal, Ezat A.; Abdelmoneim, Ahmed; Alanazi, Mohammed M.; Elshazly, Amal Mahmoud ElSafy

doi:10.3390/cells12070994

Cited by 3 publications

(1 citation statement)

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“…However, a drastic change in the proportion of polarized macrophages was found in humans and mice with allergic asthma or lung inflammation; MHCII-hi macrophages (M1) and CD206 + macrophages (M2) both increased, but interleukin (IL)-10 + macrophages decreased ( Draijer et al, 2022 ) suggesting a relationship between asthma and macrophages. CD86 and CD206 are key markers that distinguish between M1 and M2 macrophages, and their expression is markedly increased in allergic asthma ( Morsi et al, 2023 ). Arginase 1 (Arg1), found in the inflammatory zone 1 (Fizz-1) is also a biomarker of M2 macrophages ( Xu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice

Ji,

Nie,

Yao

et al. 2024

PeerJ

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Background Allergic asthma is the most prevalent asthma phenotype and is associated with the disorders of immune cells and glycolysis. Macrophages are the most common type of immune cells in the lungs. Calprotectin (S100A8 and S100A9) are two pro-inflammatory molecules that target the Toll-like receptor 4 (TLR4) and are substantially increased in the serum of patients with severe asthma. This study aimed to determine the effects of S100A8/A9 on macrophage polarization and glycolysis associated with allergic asthma. Methods To better understand the roles of S100A8 and S100A9 in the pathogenesis of allergic asthma, we used ovalbumin (OVA)-induced MH-S cells, and OVA-sensitized and challenged mouse models (wild-type male BALB/c mice). Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, flow cytometry, hematoxylin-eosin staining, and western blotting were performed. The glycolysis inhibitor 3-bromopyruvate (3-BP) was used to observe changes in glycolysis in mice. Results We found knockdown of S100A8 or S100A9 in OVA-induced MH-S cells inhibited inflammatory cytokines, macrophage polarization biomarker expression, and pyroptosis cell proportion, but increased anti-inflammatory cytokine interleukin (IL)-10 mRNA; also, glycolysis was inhibited, as evidenced by decreased lactate and key enzyme expression; especially, knockdown of S100A8 or S100A9 inhibited the activity of TLR4/myeloid differentiation primary response gene 88 (MyD88)/Nuclear factor kappa-B (NF-κB) signaling pathway. Intervention with lipopolysaccharides (LPS) abolished the beneficial effects of S100A8 and S100A9 knockdown. The observation of OVA-sensitized and challenged mice showed that S100A8 or S100A9 knockdown promoted respiratory function, improved lung injury, and inhibited inflammation; knockdown of S100A8 or S100A9 also suppressed macrophage polarization, glycolysis levels, and activation of the TLR4/MyD88/NF-κB signaling pathway in the lung. Conversely, S100A9 overexpression exacerbated lung injury and inflammation, promoting macrophage polarization and glycolysis, which were antagonized by the glycolysis inhibitor 3-BP. Conclusion S100A8 and S100A9 play critical roles in allergic asthma pathogenesis by promoting macrophage perturbation and glycolysis through the TLR4/MyD88/NF-κB signaling pathway. Inhibition of S100A8 and S100A9 may be a potential therapeutic strategy for allergic asthma.

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Section: Introductionmentioning

confidence: 99%

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice

Ji,

Nie,

Yao

et al. 2024

PeerJ

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Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone)

Manawy,

Faruk,

Hindawy

et al. 2024

Tissue and Cell

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Respiratory system: Highly exposed yet under-reported organ in pyrethrin and pyrethroid toxicity

Tewari

2024

Toxicol Ind Health

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Pyrethrin and pyrethroid are a relatively new class of pesticides with potent insecticidal properties. Pyrethrins are naturally occurring pesticides obtained from the Chrysanthemum cinerariaefolium flower, while pyrethroids are their synthetic derivatives. They are widely used as the insecticides of choice in agriculture, veterinary medicine, public health programs, and household activities. Pyrethrin, being a broad-spectrum insecticide kills a wide range of pests, while pyrethroids last longer in the environment owing to low susceptibility to sunlight, and greater stability and efficacy than parent molecules. Humans can be exposed through inhalation, ingestion, and dermal routes. Indoor usage of an insecticide poses a serious risk to human health, especially to women, children, and stay-at-home people. Although pyrethrin and pyrethroid are generally considered safe, sustained skin or inhalation exposure or direct contact with open wounds results in higher toxicity to mammals. There is a paucity of data on the impact of pyrethrin and pyrethroid on overall pulmonary health. The respiratory system, from the nose, nasal passages, airways, and bronchi to the pulmonary alveoli, is vulnerable to environmental contaminants such as pesticides because of its anatomical location as well as being a highly blood profused organ. Under and over-functioning of the respiratory system triggers diverse pathologies such as serious infections, allergies, asthma, metastatic malignancies, and auto-immune conditions. While the association between workplace-related pesticide exposures and respiratory diseases and symptoms is well documented, it is important to understand the adverse health impact of pyrethrin and pyrethroid on the general population for awareness and also for better regulation and implementation of the law.

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Modeling the Effects of Cypermethrin Toxicity on Ovalbumin-Induced Allergic Pneumonitis Rats: Macrophage Phenotype Differentiation and p38/STAT6 Signaling Are Candidate Targets of Pirfenidone Treatment

Cited by 3 publications

References 35 publications

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice

Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone)

Respiratory system: Highly exposed yet under-reported organ in pyrethrin and pyrethroid toxicity

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