Dataset Information

Particulate matter₁₀-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

ABSTRACT:

Background

Particulate matter₁₀ (PM₁₀) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM₁₀-treated murine mice models.

Methods

In female BALB/c mice, PM₁₀ was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered. Chitinase-1 inhibitor (CPX) 6 times over 3 weeks or dexamethasone 3 times in the last week were intraperitoneally administered. Two days after the last challenges, mice were euthanized. Messenger RNA sequencing using lung homogenates was conducted to evaluate signaling pathways.

Results

PM₁₀ and/or OVA-induced airway inflammation and fibrosis murine models were established. CPX and dexamethasone ameliorated PM₁₀ or PM₁₀/OVA-induced airway hyper-responsiveness, airway inflammation, and fibrosis. CPX and dexamethasone also reduced levels of various inflammatory markers in lung homogenates. PM₁₀ and OVA also induced changes in mRNA expression across an extreme range of genes. CPX and dexamethasone decreased levels of mRNA expression especially associated with inflammation and immune regulation. They also significantly regulated asthma and asthma-related pathways, including the JACK-STAT signaling pathway.

Conclusions

Chitinase-1 suppression by CPX can regulate PM₁₀- and OVA-induced and aggravated airway inflammation and fibrosis via an asthma-related signaling pathway.

SUBMITTER: Choi YJ

PROVIDER: S-EPMC10024831 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Particulate matter<sub>10</sub>-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

Choi Yong Jun YJ Han Heejae H Lee Jae-Hyun JH Lee Jaeuk J Kim Chi Young CY Byun Min Kwang MK Cho Jae Hwa JH Park Hye Jung HJ

Respiratory research 20230318 1

<h4>Background</h4>Particulate matter<sub>10</sub> (PM<sub>10</sub>) can induce airway inflammation and fibrosis. Recently, chitinase-1 has been shown to play key roles in inflammation and fibrosis. We aimed to investigate the effects of chitinase-1 inhibitor in PM<sub>10</sub>-treated murine mice models.<h4>Methods</h4>In female BALB/c mice, PM<sub>10</sub> was intranasally administered six times over 3 weeks, and ovalbumin (OVA) was intraperitoneally injected and then intranasally administered ...[more]

PMID: 36934237

Similar Datasets

Project description:Particulate matter (PM) exposure can adversely affect respiratory function. Probiotics can alleviate the inflammatory responses in respiratory diseases. We examined the protective effects of Lactobacillus paracasei ATG-E1 isolated from the feces of a newborn baby against airway inflammation in a PM10 plus diesel exhaust particle (DEP) (PM10D)-induced airway inflammation model. BALB/c mice were exposed to PM10D by intranasal injection three times at 3-day intervals for 12 days, and L. paracasei ATG-E1 was administered orally for 12 days. Analysis of immune cell population and expression of various inflammatory mediators and gut barrier-related genes were determined in bronchoalveolar lavage fluid (BALF), lung, peyer's patch, and small intestine. A histological analysis of the lungs was performed. In addition, the in vitro safety and their safety in genomic analyses were examined. L. paracasei ATG-E1 was found to be safe in vitro and by genomic analysis. L. paracasei ATG-E1 suppressed neutrophil infiltration and the number of CD4+, CD4+CD69+, CD62L-CD44+high, CD21/35+B220+, and Gr-1+CD11b+ cells, as well as the expression of inflammatory mediators, including chemokine (C-X-C motif) ligand (CXCL)-1, macrophage inflammatory protein (MIP)-2, interleukin (IL)-17a, tumor necrosis factor (TNF)-α, and IL-6 in BALF and lungs in PM10D-induced airway inflammation. It protected against histopathological damage in the lungs of mice with PM10D-induced airway inflammation. L. paracasei ATG-E1 concomitantly increased the expression levels of the gut barrier function-related genes occludin, claudin-1, and IL-10 in the small intestine, with an increased number of CD4+ and CD4+CD25+ immune cells in the peyer's patch. L. paracasei ATG-E1 suppressed immune activation and airway inflammatory responses in the airways and lungs by restoring the lung damage by PM10D. It also regulated intestinal immunity and ameliorated the gut barrier function in the ileum. These results indicate the potential of L. paracasei ATG-E1 as an protective and therapeutic agent against airway inflammation and respiratory diseases.

Project description:Particulate matter (PM) is able to induce airway epithelial injury, while the detailed mechanisms remain unclear. Here we demonstrated that PM exposure inactivated MTOR (mechanistic target of rapamycin kinase), enhanced macroautophagy/autophagy, and impaired lysosomal activity in HBE (human bronchial epithelial) cells and in mouse airway epithelium. Genetic or pharmaceutical inhibition of MTOR significantly enhanced, while inhibition of autophagy attenuated, PM-induced IL6 expression in HBE cells. Consistently, club-cell-specific deletion of Mtor aggravated, whereas loss of Atg5 in bronchial epithelium reduced, PM-induced airway inflammation. Interestingly, the augmented inflammatory responses caused by MTOR deficiency were markedly attenuated by blockage of downstream autophagy both in vitro and in vivo. Mechanistically, the dysregulation of MTOR-autophagy signaling was partially dependent on activation of upstream TSC2, and interacted with the TLR4-MYD88 to orchestrate the downstream NFKB activity and to regulate the production of inflammatory cytokines in airway epithelium. Moreover, inhibition of autophagy reduced the expression of EPS15 and the subsequent endocytosis of PM. Taken together, the present study provides a mechanistic explanation for how airway epithelium localized MTOR-autophagy axis regulates PM-induced airway injury, suggesting that activation of MTOR and/or suppression of autophagy in local airway might be effective therapeutic strategies for PM-related airway disorders.Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; ALI: air liquid interface; AP2: adaptor related protein complex 2; ATG: autophagy related; BALF: bronchoalveolar lavage fluid; COPD: chronic obstructive pulmonary disease; CXCL: C-X-C motif chemokine ligand; DOX: doxycycline; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPS15: epidermal growth factor receptor pathway substrate 15; HBE: human bronchial epithelial; H&E: hematoxylin & eosin; IKK: IKB kinase; IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTEC: mouse tracheal epithelial cells; MTOR: mechanistic target of rapamycin kinase; MYD88: MYD88 innate immune signal transduction adaptor; NFKB: nuclear factor of kappa B; NFKBIA: NFKB inhibitor alpha; PM: particulate matter; PtdIns3K: phosphatidylinositol 3-kinase; Rapa: rapamycin; RELA: RELA proto-oncogene, NFKB subunit; SCGB1A1: secretoglobin family 1A member 1; siRNA: small interfering RNAs; SQSTM1: sequestosome 1; TEM: transmission electronic microscopy; TLR4: toll like receptor 4; TSC2: TSC complex subunit 2.

Dataset Information

Particulate matter₁₀-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

Background

Methods

Results

Conclusions

Publications

Particulate matter<sub>10</sub>-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Particulate matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

Background

Methods

Results

Conclusions

Publications

Particulate matter<sub>10</sub>-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Particulate matter₁₀-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression.