Interleukin 1 receptor regulates miRNA-135b expression in a negative feedback mechanism during cigarette smoke-induced inflammation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE43688 | GEO | 2013/01/31
SECONDARY ACCESSION(S): PRJNA187170
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-31 | E-GEOD-43688 | biostudies-arrayexpress
Project description:Although microRNA-135b (miR-135b) is known to be associated with cancer, with recent work showing that it is massively induced in the pulmonary tissues of mice challenged with nanoparticles suggests a critical role for this microRNA in mediating inflammatory response. In this study, we investigated the expression and function of miR-135b in mice exposed to cigarette smoke or nontypeable Haemophilus influenzae (NTHi). Exposure to both cigarette smoke and NTHi elicited robust lung inflammation, but increased miR-135b expression was observed only in the lungs of cigarette smoke-exposed mice. Using IL-1R 1 knockout mice, we show that miR-135b expression is IL-1R1 dependent. A series of in vitro experiments confirmed the role of IL-1R1 in regulating miR-135b expression. In vitro activation of the IL-1R1 pathway in mouse embryonic fibroblast (NIH3T3) and lung epithelial (FE1) cells resulted in increased miR-135b, which was blocked by IL-1R1 antagonists or small interfering RNA-mediated silencing of IL-1R1 expression. Overexpression of mature miR-135b in NIH3T3 cells (pEGP-mmu-mir-135b) resulted in the suppression of endogenous levels of IL-1R1 expression. pEGP-mmu-miR-135b cells transiently transfected with luciferase reporter vector containing the 3'UTR of mouse IL-1R1 showed reduced luciferase activity. Finally, we demonstrate that miR-135b targets IL-1-stimulated activation of Caspase-1, the IL-1R1 downstream activator of IL-1? leading to suppressed synthesis of the active form of IL-1? protein. These results suggest that miR-135b expression during cigarette smoke-induced inflammation is regulated by IL-1R1 in a regulatory feedback mechanism to resolve inflammation.
| S-EPMC3607400 | biostudies-literature
Project description:RT-PCR analysis of inflammatory cytokines and receptors in pEGP-miR-135b over-expressing cells compard to controls (pEGP-miR-null) using pathway-specific PCR arrays for the evaluation of mouse inflammatory cytokines and receptors (#PAMM-011D).
2013-01-31 | GSE43681 | GEO
Project description:RT-PCR analysis of inflammatory cytokines and receptors in pEGP-miR-135b over-expressing cells compard to controls (pEGP-miR-null) using pathway-specific PCR arrays for the evaluation of mouse inflammatory cytokines and receptors (#PAMM-011D). qPCR array gene expression profiling. This experiment examined the transcriptional response of NIH3T3 cells over-expressing pEGP-miR-135b. Total RNA (n = 3 per group) was used with SABiosciences pathway-specific PCR arrays for inflammatory cytokines and receptors (#PAMM-011D).
2013-01-31 | E-GEOD-43681 | biostudies-arrayexpress
Project description:RT-PCR analysis of inflammatory cytokines and receptors following Il1alpha treatment of pEGP-miR-135b over-expressing cells compard to controls (pEGP-miR-null) using pathway-specific PCR arrays for the evaluation of mouse inflammatory cytokines and receptors (#PAMM-011D).
2013-01-31 | GSE43683 | GEO
Project description:RT-PCR analysis of inflammatory cytokines and receptors following Il1alpha treatment of pEGP-miR-135b over-expressing cells compard to controls (pEGP-miR-null) using pathway-specific PCR arrays for the evaluation of mouse inflammatory cytokines and receptors (#PAMM-011D). qPCR array gene expression profiling. This experiment examined the transcriptional response of NIH3T3 cells over-expressing pEGP-miR-135b following IL1alpha treatment. Total RNA (n = 3 per group) was used with SABiosciences pathway-specific PCR arrays for inflammatory cytokines and receptors (#PAMM-011D).
2013-01-31 | E-GEOD-43683 | biostudies-arrayexpress
Project description:Cigarette smoke (CS)-induced inflammation leads to a range of diseases including chronic obstructive pulmonary disease and cancer. The gut microbiota is a major modifying environmental factor that determine the severity of cigarette smoke-induced pathology. Microbiomes and metabolites from CS-exposed mice exacerbate lung inflammation via the gut-lung axis of shared mucosal immunity in mice but these systems are expensive to establish and analyse. Zebrafish embryos and larvae have been used to model the effects of cigarette smoking on a range of physiological processes and offer an amenable platform for screening modifiers of cigarette smoke-induced pathologies with key features of low cost and rapid visual readouts. Here we exposed zebrafish larvae to cigarette smoke extract (CSE) and characterised a CSE-induced leukocytic inflammatory phenotype with increased neutrophilic and macrophage inflammation in the gut. The CSE-induced phenotype was exacerbated by co-exposure to microbiota from the faeces of CS-exposed mice, but not control mice. Microbiota could be recovered from the gut of zebrafish and studied in isolation in a screening setting. This demonstrates the utility of the zebrafish-CSE exposure platform for identifying environmental modifiers of cigarette smoking-associated pathology and demonstrates that the CS-exposed mouse gut microbiota potentiates the inflammatory effects of CSE across host species.
| S-EPMC9040087 | biostudies-literature
Project description:BackgroundCigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation.MethodsWe developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated.ResultsSmoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression.ConclusionsOur findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a "smoke sensor" for bone remodeling.
| S-EPMC8061040 | biostudies-literature
Project description:The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an in vitro model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression of MUC5AC, TGF-β1, and MMP-9 mRNAs was measured before and after losartan treatment. In vitro, CS exposure of HBECs caused a significant increase in mRNA expression of MUC5AC and TGF-β1 and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease in MUC5AC expression and mucus concentrations, partially by inhibiting TGF-β signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels of MUC5AC, TGF-β1, and MMP-9 in the upper airways after 2 months of losartan treatment. Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases.
| S-EPMC7836504 | biostudies-literature
Project description:(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.
| S-EPMC8151076 | biostudies-literature