Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-α/NF-κB signal and the activities of MMP-2 and MMP-9

Cigarette smoke exposure causes vascular remodeling and pulmonary hypertension by poorly understood mechanisms. To ascertain whether cigarette smoke exposure affects production of matrix metalloproteinases (MMPs) in the pulmonary vessels, we exposed C57Bl/6 (C57) mice or mice lacking TNF-α receptors (TNFRKO) to smoke daily for 2 wk or 6 mo. Using laser capture microdissection and RT-PCR analysis, we examined gene expression of MMP-2, MMP-9, MMP-12, MMP-13, and tissue inhibitor of metalloproteinase (TIMP-1) and examined protein production by immunohistochemistry for MMP-2, MMP-9, and MMP-12 in small intrapulmonary arteries. At 2 wk, mRNA levels of TIMP-1 and all MMPs were increased in the C57, but not TNFRKO, mice, and immunoreactive protein for MMP-2, MMP-9, and MMP-12 was also increased in the C57 mice. Increased gelatinase activity was identified by in situ and bulk tissue zymography. At 6 mo, only MMP-12 mRNA levels remained increased in the C57 mice, but at a much lower level; however, MMP-2 mRNA levels increased in the TNFRKO mice. We conclude that smoke exposure increases MMP production in the small intrapulmonary arteries but that, with the exception of MMP-12, increased MMP production is transient. MMPs probably play a role in smoke-induced vascular remodeling, as they do in other forms of pulmonary hypertension, implying that MMP inhibitors might be beneficial. MMP production is largely TNF-α dependent, further supporting the importance of TNF-α in the pathogenesis of cigarette smoke-induced lung disease.

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P2‐29: Short‐term intermittent cigarette smoke exposure enhances the stemness of alveolar type 2 cells through activation of fatty acid oxidation

Respirology ◽

10.1111/resp.14150_125 ◽

2021 ◽

Vol 26 (S3) ◽

pp. 124-124

Keyword(s):

Fatty Acid ◽

Cigarette Smoke ◽

Fatty Acid Oxidation ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Acid Oxidation ◽

Alveolar Type ◽

Short Term

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Short-term regulation of the hepatic activities of cytochrome P450 and glutathione S-transferase by nose-only cigarette smoke exposure in mice

Food and Chemical Toxicology ◽

10.1016/j.fct.2018.12.035 ◽

2019 ◽

Vol 125 ◽

pp. 182-189 ◽

Cited By ~ 2

Author(s):

Chang Seon Ryu ◽

Young Jae Choi ◽

Hyo Seon Nam ◽

Jang Su Jeon ◽

Taeyoon Jung ◽

...

Keyword(s):

Cytochrome P450 ◽

Cigarette Smoke ◽

Smoke Exposure ◽

Cigarette Smoke Exposure ◽

Glutathione S Transferase ◽

Short Term

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Liver growth factor treatment reverses emphysema previously established in a cigarette smoke exposure mouse model

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00293.2013 ◽

2014 ◽

Vol 307 (9) ◽

pp. L718-L726 ◽

Cited By ~ 10

Author(s):

Sandra Pérez-Rial ◽

Laura del Puerto-Nevado ◽

Álvaro Girón-Martínez ◽

Raúl Terrón-Expósito ◽

Juan J. Díaz-Gil ◽

...

Keyword(s):

Growth Factor ◽

Cigarette Smoke ◽

Systemic Inflammation ◽

Smoke Exposure ◽

Lung Damage ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Liver Growth ◽

Tnf Α ◽

Α Level

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD.

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