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- 01GJ2QRWEVZS5MW9BW2MH0CCT6 classification A1.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 date "2022".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 language "eng".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 type journalArticle.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 hasPart 01GJ2QTHMQSQA41HCHP4AM2Y53.pdf.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 subject "Medicine and Health Sciences".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 doi "10.1183/13993003.01431-2021".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 issn "0903-1936".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 issn "1399-3003".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 issue "6".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 volume "60".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 abstract "BACKGROUND: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase-1 (hCMA1) and it's ortholog mCMA1/mouse mast cell (MC) protease-5 (mMCP5) are exocytosed from activated MCs and have adverse roles in numerous disorders, but their role in COPD is unknown.; METHODS: We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5-deficient (-/-) mice to evaluate this proteases' role and potential for therapeutic targeting in CS-induced experimental COPD. We also used ex vivo/in vitro studies to define mechanisms.; RESULTS: The levels of hCMA1 mRNA and CMA1+ MCs were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated MC numbers and mMCP5 protein were increased in lung tissues of wild-type (WT) mice with experimental COPD. mmcp5 -/- mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of MCs from WT but not mmcp5 -/- mice with WT lung macrophages increased in TNF-alpha release. It also caused the release of CMA1 from human MCs, and recombinant hCMA-1 induced TNF-alpha release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.; CONCLUSION: CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-alpha expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD. Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author 358D04BC-F0EE-11E1-A9DE-61C894A0A6B4.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author F640E850-F0ED-11E1-A9DE-61C894A0A6B4.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:21b716f2-776f-42bc-8311-4fdb8af6c5fd.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:2bd4720c-cc05-4b25-b6d1-be5849cd9d9a.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:3bc2f57d-f640-4e52-9237-691e272e5402.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:615d5be3-fbe7-41b4-a8ff-f7f73739ff0c.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:626ccbba-f6aa-4050-83d8-acd0f2f99de7.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:684d3aa1-e885-4a21-ba02-6a145650fabb.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:6eb77010-9756-4ace-83d9-a1ca07336602.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:76eb9e45-e72c-45eb-bc53-1538645a08cf.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:7ca7e2cf-9d44-4f35-8c0d-1119a0144362.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:7f2baea8-4582-4f3e-854c-0438274d9823.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:81de9a6e-62c4-41ec-a061-6d5d9c6e5478.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:99a30456-1292-4d8d-bcb3-831c6e7c2039.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:9d1fbc3b-a09a-4d1b-82ac-12681ba5e633.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:9eabded5-8d8d-43b8-9b00-6101eb2f5873.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:9f9d544d-6cd1-4de4-967a-ac762c451045.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:ae5b5935-5949-4b9a-81dc-f9377e301cda.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:cd603dce-f21c-4c94-8da2-32a6841b12fb.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:e0862ed8-e2c2-4df6-b538-929e382b8419.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:e2b9c134-bcd3-485e-8113-44367c29ae27.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:e3313db2-d1c0-4dfb-8060-b43fe647677b.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:ee6c775a-458c-476d-af9f-64077ad68b76.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 author urn:uuid:f875bb52-2c04-4390-b0c8-da650bb3a7ef.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 dateCreated "2022-11-17T12:07:16Z".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 dateModified "2024-10-29T16:04:48Z".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 name "Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease".
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 pagination urn:uuid:af73e502-dab7-4521-9092-7570e4e297cd.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 sameAs LU-01GJ2QRWEVZS5MW9BW2MH0CCT6.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 sourceOrganization urn:uuid:a894987b-24b1-406d-8cd5-2ac060839c90.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 sourceOrganization urn:uuid:d62c09d8-0bfb-4c15-b60c-c90af32c3276.
- 01GJ2QRWEVZS5MW9BW2MH0CCT6 type A1.