Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System

Morales-Mantilla, Daniel E.; Huang, Xinyan; Erice, Philip; Porter, Paul B.; Zhang, Yun; Figueroa, Mary; Chandra, Joya; King, Katherine Y.; Kheradmand, Farrah; Rodriguez, Antony

doi:10.3791/61793

Cited by 10 publications

(16 citation statements)

References 17 publications

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“…To promote emphysema, mice were exposed to cigarette smoke using our custom designed whole-body inhalation system (Morales-Mantilla et al, 2020). In total, mice were exposed to four cigarettes (Marlboro 100’s; Philip Morris USA) per day, five days a week, for four months as previously described (Morales-Mantilla et al, 2020, Shan et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…For histomorphometric analysis, mice lungs were fixed with 10% neutral-buffered formalin solution via a tracheal cannula at 25-cm H 2 O pressure followed by paraffin embedding and tissue sectioning and stained with hematoxylin and eosin. Mean linear intercept (MLI) measurement of mouse lung morphometry were done as previously described (Shan et al, 2014; Morales-Mantilla et al, 2020). Briefly, this was done in a blinded fashion to mice genotypes from ten randomly selected fields of lung parenchyma sections.…”

Section: Methodsmentioning

confidence: 99%

“…BALF was collected by instilling and withdrawing 0.8 ml of sterile PBS twice through the trachea. Total and differential cell counts in the BALF were determined with the standard hemocytometer and HEMA3 staining (Biochemical Sciences Inc, Swedesboro, NJ) using 200 μL of BALF for cytospin slide preparation (Morales-Mantilla et al, 2020; W. Lu et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

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Downregulation ofLet-7miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Erice,

Huang,

Seasock

et al. 2023

Preprint

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Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. Thelet-7family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests thelet-7family is downregulated in patients with COPD, however, how they cause emphysema remains unclear. Here we show that overall expression of thelet-7miRNA clusters,let-7b/let-7c2andlet-7a1/let-7f1/let-7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of thelet-7b/let-7c2-cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of thelet-7b/let-7c2-clusterenhanced CD8+IL17a+T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressinglet-7in T cells were resistant to Tc17 and CD4+T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target oflet-7miRNA in T cells. Overall, our findings support of thelet-7/RORγt as a driver and braking regulatory circuit in the generation of Tc17 cells, suggesting novel therapeutic approaches for tempering the augmented IL-17-mediated response in emphysema.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Downregulation ofLet-7miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Erice,

Huang,

Seasock

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…To promote emphysema, mice were exposed to cigarette smoke using our custom designed wholebody inhalation system (Morales-Mantilla et al, 2020 ). In total, mice were exposed to four cigarettes (Marlboro 100's; Philip Morris USA) per day, five days a week, for four months as previously described (Morales-Mantilla et al, 2020.…”

Section: Cigarette Smoke Exposure Model Of Pulmonary Emphysemamentioning

confidence: 99%

Downregulation of Let-7 miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Erice,

Huang,

Seasock

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the let-7 family is downregulated in patients with COPD, however, how they cause emphysema remains unclear. Here we show that overall expression of the let-7 miRNA clusters, let-7b/let-7c2 and let-7a1/let-7f1/let-7d , are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the let-7b/let-7c2- cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the let-7b/let-7c2-cluster enhanced CD8 + IL17a + T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing let-7 in T cells were resistant to Tc17 and CD4 + T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of let-7 miRNA in T cells. Overall, our findings shed light on the let-7 /RORγt axis as a braking and driving regulatory circuit in the generation of Tc17 cells and suggests a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

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“…Cigarette smoke exposure to mice was carried out in an exposure chamber (31 x 19 x 22 cm) which had two holes, each for smoke input and output. Cigarette smoke was derived from a clove cigarette per day (Morales-Mantilla et al, 2020). On day 37, all mice were euthanized by cervical dislocation and dissected to collect the testes and cauda epididymis.…”

Section: Treatment Of Animalsmentioning

confidence: 99%

Green tea (Camellia sinensis) leaf extract maintained spermatozoa plasma membrane integrity, viability, and motility of mice (Mus musculus) exposed to cigarette smoke

Silviani¹,

Sukmanadi²,

Kurnijasanti³

et al. 2022

Ovz

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Cigarette smoke chemicals caused oxidative stress by increasing Reactive Oxygen Species (ROS). ROS exposure could be neutralized by antioxidants, such as green tea (Camellia sinensis) leaf extract. This study aimed to determine the effect of green tea extract (GTE) on spermatozoa plasma membrane integrity, spermatozoa viability, and spermatozoa motility of mice (Mus musculus) exposed to cigarette smoke. Twenty-five mice were randomly divided into five groups. Group C- mice were given a placebo (1% Sodium carboxymethyl cellulose, Na-CMC). Group C+, T1, T2, and T3 mice were exposed to cigarette smoke and given 0, 20, 40, and 60 mg/kg BW GTE respectively. Cigarette smoke exposure used a clove cigarette per day. GTE in 1% Na-CMC solution was administered at 0.5 mL orally using a gastric probe. The treatment was conducted daily for 36 days, and on day 37, all mice were euthanized for spermatozoa evaluation. The results showed that all parameters evaluated in the C+ group were lower (p <0.05) than in C- group. Administration of GTE in the T2 group increased (p <0.05) all parameters compared to mice in the C+ group. However, administration of GTE to mice in the T3 group caused a decrease (p <0.05) in all parameters than those of the T2 group and was not significantly different (p >0.05) compared to those of the C+ group. It could be concluded that the administration of GTE at 40 mg/kg BW has maintained the spermatozoa plasma membrane integrity, spermatozoa viability, and spermatozoa motility of mice exposed to cigarette smoke.

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Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System

Cited by 10 publications

References 17 publications

Downregulation ofLet-7miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Downregulation ofLet-7miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Downregulation of Let-7 miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt

Green tea (Camellia sinensis) leaf extract maintained spermatozoa plasma membrane integrity, viability, and motility of mice (Mus musculus) exposed to cigarette smoke

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