ArticleThe Journal of biological chemistry2011
TLR4 protein contributes to cigarette smoke-induced matrix metalloproteinase-1 (MMP-1) expression in chronic obstructive pulmonary disease.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters.Respiratory research · 2014Trial
- Aged Garlic Extract and Its Bioactive Molecules S-Allyl-Cysteine and S1-Propenyl-Cysteine: A Review Focusing on Evidences Supporting Their Use for Mitigating the Effects of Cigarette Smoking.Molecules (Basel, Switzerland) · 2025Review
- The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis.International journal of molecular sciences · 2023Review
- Impact of Previous Pulmonary Tuberculosis on Chronic Obstructive Pulmonary Disease: Baseline Results from a Prospective Cohort Study.Combinatorial chemistry & high throughput screening · 2023Article
- Extracellular Vesicles' Role in the Pathophysiology and as Biomarkers in Cystic Fibrosis and COPD.International journal of molecular sciences · 2022Review
- Expanding role of deoxyribonucleic acid-sensing mechanism in the development of lifestyle-related diseases.Frontiers in cardiovascular medicine · 2022Review
- Suppression of cigarette smoke induced MMP1 expression by selective serotonin re-uptake inhibitors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration.The Laryngoscope · 2021Article
- Epithelial Barrier Dysfunction in Chronic Respiratory Diseases.Frontiers in physiology · 2021Review
- The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases.Pulmonary medicine · 2021Review
- Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Regulation of ATP binding cassette transporter A1 (ABCA1) expression: cholesterol-dependent and - independent signaling pathways with relevance to inflammatory lung disease.Respiratory research · 2020Review
- Apolipoprotein E Signals via TLR4 to Induce CXCL5 Secretion by Asthmatic Airway Epithelial Cells.American journal of respiratory cell and molecular biology · 2020Article
- Immunogenicity and Toxicity of Different Adjuvants Can Be Characterized by Profiling Lung Biomarker Genes After Nasal Immunization.Frontiers in immunology · 2020Article
- Single-photon emission computed tomography/computed tomography imaging of RAGE in smoking-induced lung injury.Respiratory research · 2019Article
- A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Cell Specific Matrix Metalloproteinase-1 Regulates Lung Metastasis Synergistically with Smoke Exposure.Journal of cancer research forecast · 2018Article
- LPS enhances TLR4 expression and IFN‑γ production via the TLR4/IRAK/NF‑κB signaling pathway in rat pulmonary arterial smooth muscle cells.Molecular medicine reports · 2017Article
- HIV infection model of chronic obstructive pulmonary disease in mice.American journal of physiology. Lung cellular and molecular physiology · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cigarette smoke is the major risk factor associated with the development of chronic obstructive pulmonary disease and alters expression of proteolytic enzymes that contribute to disease pathology. Previously, we reported that smoke exposure leads to the induction of matrix metalloproteinase-1 (MMP-1) through the activation of ERK1/2, which is critical to the development of emphysema. To date, the upstream signaling pathway by which cigarette smoke induces MMP-1 expression has been undefined. This study demonstrates that cigarette smoke mediates MMP-1 expression via activation of the TLR4 signaling cascade. In vitro cell culture studies demonstrated that cigarette smoke-induced MMP-1 was regulated by TLR4 via MyD88/IRAK1. Blockade of TLR4 or inhibition of IRAK1 prevented cigarette smoke induction of MMP-1. Mice exposed to acute levels of cigarette smoke exhibited increased TLR4 expression. To further confirm the in vivo relevance of this signaling pathway, rabbits exposed to acute cigarette smoke were found to have elevated TLR4 signaling and subsequent MMP-1 expression. Additionally, lungs from smokers exhibited elevated TLR4 and MMP-1 levels. Therefore, our data indicate that TLR4 signaling, through MyD88 and IRAK1, plays a predominant role in MMP-1 induction by cigarette smoke. The identification of the TLR4 pathway as a regulator of smoke-induced protease production presents a series of novel targets for future therapy in chronic obstructive pulmonary disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.