Ovary-dependent emphysema augmentation and osteopontin induction in adult female mice

Niikura, Yuichi; Ishii, Takashi; Hosoki, Keisuke; Nagase, Takahide; Yamashita, Naomi

doi:10.1016/j.bbrc.2015.04.081

Cited by 9 publications

(10 citation statements)

References 32 publications

(36 reference statements)

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“…Female-derived factors contribute to the development and progression of inflammatory diseases. We previously demonstrated the female-specific augmentation of experimental emphysema in 2-month-old mice [57]. We found that ovariectomy significantly reduced acute neutrophilic airway inflammation and subsequent alveolar destruction in elastase-treated female mice, indicating that the ovaries actively contribute to the pathogenesis of emphysema in adult females.…”

Section: Discussionmentioning

confidence: 73%

“…Sensitized female mice aged 8 weeks were anesthetized by intraperitoneal injection of a ketamine–medetomidine cocktail (55 mg/kg and 0.4 mg/kg, respectively) and underwent bilateral ovariectomy via a dorsolateral approach [57]. Ovariectomy was performed at least 4 weeks before the first OVA challenge to ensure the absence of endogenous ovarian hormones.…”

Section: Methodsmentioning

confidence: 99%

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Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific

Niikura

Ishii

Murakami

et al. 2019

Aging

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Reproductive organs play a pivotal role in asthma development and progression, especially in women. Endocrine environment changes associated with the menstrual cycle, pregnancy, and menopause can exacerbate the clinical features of asthma. Factors secreted by reproductive organs may be responsible for the gender difference and age-related changes in adult asthma. Here, we show that mammalian seminal fluid has anti-asthma effects exclusively in females. Exposure to murine seminal fluid markedly reduced eosinophilic airway inflammation in 2-month-old female mice upon ovalbumin inhalation. The anti-asthma effect with seminal fluid from 10-month-old males was double that with fluid from 2-month-old males, suggesting that it depended on male sexual maturation. We further found that seminal fluid from middle-aged human volunteers had beneficial effects in asthmatic female mice; these effects were associated with transcriptional repression of osteopontin and IL-17A, which are poor prognostic factors for asthma. In 2-month-old male mice, however, human seminal fluid failed to decrease asthmatic features and even enhanced osteopontin and IL-17A transcription. Our data demonstrate that age-related seminal fluid exerts opposing effects in asthmatic male and female mice. These findings may help the development of novel approaches to control the prevalence and age-related progression of asthma in women.

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Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific

Niikura

Ishii

Murakami

et al. 2019

Aging

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“…Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and emphysema that is usually associated with a turgescent chronic inflammatory response in the airways and the lung ( Chung and Adcock, 2008 ). Inflammation with infiltrating various inflammatory cells such as macrophages, neutrophils and lymphocytes, is a pivotal contributing factor in the COPD development and is believed to be closely related to emphysema and pathologic alterations, which further worsen with this disease progression ( Niikura et al, 2015 ; Kang and Shadel, 2016 ). Hence, we firstly investigated the effect of STS on CS-induced inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway

Guan

Wang

et al. 2018

Front. Pharmacol.

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Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α–induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and inhibition of these signaling molecules significantly repressed CSE-induced HIF-1α expression. It indicated that STS inhibits CSE-induced HIF-1α expression likely by blocking MAPK signaling. Furthermore, STS also promoted HIF-1α protein degradation in CSE-stimulated macrophages. Taken together, these results suggest that STS prevents COPD development possibly through the inhibition of HIF-1α signaling, and may be a novel strategy for the treatment of COPD.

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“…At week 6, mice were euthanized, a tracheal cannula was inserted, and the lungs were inflated with 4% paraformaldehyde for fixation, paraffin embedded, and cut in 5-mm sections. To histopathologically assess emphysema formation, we stained the lung sections with H&E and calculated the mean linear intercept, as previously described (19,20).…”

Section: Lung Histopathology and Measurement Of Mean Linear Interceptmentioning

confidence: 99%

“…Differential cell counts were performed on cytospin preparations stained with Diff-Quik (Sysmex, Hyogo, Japan) according to the manufacturer's instructions. The methods for total RNA extraction from harvested lungs, cDNA synthesis, and quantitative PCR have been previously described (20). The expression of genes of interest was calculated according to the comparative threshold cycle method, using b-actin as an internal control.…”

Section: Bronchoalveolar Lavage Fluid Analysis and Quantitative Real-mentioning

confidence: 99%

IFN Regulatory Factor 3 Potentiates Emphysematous Aggravation by Lipopolysaccharide

Ishii

Hosoki

Nikura

et al. 2017

The Journal of Immunology

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Acute exacerbation of chronic obstructive pulmonary disease (COPD) is often induced by infection and often has a poor prognosis. Bacterial LPS activates innate immune receptor TLR4 followed by activation of a transcriptional factor IFN regulatory factor-3 (IRF3) as well as NF-κB, resulting in upregulation of various inflammatory mediators. To clarify the role of IRF3 in the pathogenesis of LPS-triggered COPD exacerbation, porcine pancreatic elastase (PPE) followed by LPS was administered intranasally to wild-type (WT) or IRF3 male mice. Sequential quantitative changes in emphysema were evaluated by microcomputed tomography, and lung histology was evaluated at the sixth week. WT mice treated with PPE and LPS exhibited enlarged alveolar spaces, whereas this feature was attenuated in similarly treated IRF3 mice. Moreover, LPS-induced emphysema aggravation was detected only in WT mice. Analysis of acute inflammation induced by PPE plus LPS revealed that the lungs of treated IRF3 mice had decreased mRNA transcripts for MCP-1, MIP-1α, TNF-α, and IFN-γ-inducible protein-10 but had increased neutrophils. IRF3 was involved in the production of mediators from macrophages, alveolar epithelial cells, and neutrophils. Furthermore, compared with isolated WT neutrophils from inflamed lung, those of IRF3 neutrophils exhibited impaired autophagic activation, phagocytosis, and apoptosis. These results suggest that IRF3 accelerated emphysema formation based on distinct profiles of mediators involved in LPS-induced COPD exacerbation. Regulation of the IRF3 pathway can affect multiple cell types and contribute to ameliorate pathogenesis of infection-triggered exacerbation of COPD.

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Ovary-dependent emphysema augmentation and osteopontin induction in adult female mice

Cited by 9 publications

References 32 publications

Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific

Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific

Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway

IFN Regulatory Factor 3 Potentiates Emphysematous Aggravation by Lipopolysaccharide

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