{"title":"博莱霉素诱导 MIP-4 并部分通过 Nir-1 受体刺激细胞迁移","authors":"M Pacurari, I Cox, A N Bible, S Davern","doi":"10.1155/2024/5527895","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>CC-chemokine ligand 18 also known as MIP-4 is a chemokine with roles in inflammation and immune responses. It has been shown that MIP-4 is involved in the development of several diseases including lung fibrosis and cancer. How exactly MIP-4 is regulated and exerts its role in lung fibrosis remains unclear. Therefore, in the present study, we examined how MIP-4 is regulated and whether it acts via its potential receptor Nir-1.</p><p><strong>Materials and methods: </strong>A549 cells were grown and maintained in DMEM : F12 (1 : 1) and supplemented with 10% FBS and 1000 U of penicillin/streptomycin and maintained as recommended by the manufacturer (ATCC). Cell migration and invasion, immunohistochemistry (IHC), Western blot, qPCR, and siRNA Nir-1 were used to determine MIP-4 regulation and its role in cell migration.</p><p><strong>Results: </strong>Cell migration was increased following stimulation of cells with recombinant (r) MIP-4 and bleomycin (BLM), whereas quenching rMIP-4 with its antibody (Ab) or addition of the Ab to BLM or H<sub>2</sub>O<sub>2</sub> diminished rMIP-4-induced cell migration. Along with cell migration, rMIP-4, BLM, and H<sub>2</sub>O<sub>2</sub> induced the formation of actin filaments dynamic structures whereas costimulation with MIP-4 Ab limited BLM- and H<sub>2</sub>O<sub>2</sub>-induced effects. MIP-4 mRNA and protein were increased by BLM and H<sub>2</sub>O<sub>2</sub>, and the addition of its Ab significantly reduced treatments effect. Experiments with siRNA investigating whether Nir-1 is a potential MIR-4 receptor indicated that the inhibition of Nir-1 decreased cell migration/invasion but did not totally inhibit rMIP-4-induced cell migration.</p><p><strong>Conclusion: </strong>Therefore, our data indicate that MIP-4 is regulated by BLM and H<sub>2</sub>O<sub>2</sub> and costimulation with its Ab limits the effects on MIP-4 and that the Nir-1 receptor partially mediates MIP-4's effects on increased cell migration. These data also evidenced that MIP-4 is regulated by fibrotic and oxidative stimuli and that quenching MIP-4 with its Ab or therapeutically targeting the Nir-1 receptor may partially limit MIP-4 effects under fibrotic or oxidative stimulation.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315970/pdf/","citationCount":"0","resultStr":"{\"title\":\"MIP-4 is Induced by Bleomycin and Stimulates Cell Migration Partially via Nir-1 Receptor.\",\"authors\":\"M Pacurari, I Cox, A N Bible, S Davern\",\"doi\":\"10.1155/2024/5527895\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>CC-chemokine ligand 18 also known as MIP-4 is a chemokine with roles in inflammation and immune responses. It has been shown that MIP-4 is involved in the development of several diseases including lung fibrosis and cancer. How exactly MIP-4 is regulated and exerts its role in lung fibrosis remains unclear. Therefore, in the present study, we examined how MIP-4 is regulated and whether it acts via its potential receptor Nir-1.</p><p><strong>Materials and methods: </strong>A549 cells were grown and maintained in DMEM : F12 (1 : 1) and supplemented with 10% FBS and 1000 U of penicillin/streptomycin and maintained as recommended by the manufacturer (ATCC). Cell migration and invasion, immunohistochemistry (IHC), Western blot, qPCR, and siRNA Nir-1 were used to determine MIP-4 regulation and its role in cell migration.</p><p><strong>Results: </strong>Cell migration was increased following stimulation of cells with recombinant (r) MIP-4 and bleomycin (BLM), whereas quenching rMIP-4 with its antibody (Ab) or addition of the Ab to BLM or H<sub>2</sub>O<sub>2</sub> diminished rMIP-4-induced cell migration. Along with cell migration, rMIP-4, BLM, and H<sub>2</sub>O<sub>2</sub> induced the formation of actin filaments dynamic structures whereas costimulation with MIP-4 Ab limited BLM- and H<sub>2</sub>O<sub>2</sub>-induced effects. MIP-4 mRNA and protein were increased by BLM and H<sub>2</sub>O<sub>2</sub>, and the addition of its Ab significantly reduced treatments effect. Experiments with siRNA investigating whether Nir-1 is a potential MIR-4 receptor indicated that the inhibition of Nir-1 decreased cell migration/invasion but did not totally inhibit rMIP-4-induced cell migration.</p><p><strong>Conclusion: </strong>Therefore, our data indicate that MIP-4 is regulated by BLM and H<sub>2</sub>O<sub>2</sub> and costimulation with its Ab limits the effects on MIP-4 and that the Nir-1 receptor partially mediates MIP-4's effects on increased cell migration. These data also evidenced that MIP-4 is regulated by fibrotic and oxidative stimuli and that quenching MIP-4 with its Ab or therapeutically targeting the Nir-1 receptor may partially limit MIP-4 effects under fibrotic or oxidative stimulation.</p>\",\"PeriodicalId\":8826,\"journal\":{\"name\":\"Biochemistry Research International\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315970/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry Research International\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2024/5527895\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry Research International","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2024/5527895","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
MIP-4 is Induced by Bleomycin and Stimulates Cell Migration Partially via Nir-1 Receptor.
Background: CC-chemokine ligand 18 also known as MIP-4 is a chemokine with roles in inflammation and immune responses. It has been shown that MIP-4 is involved in the development of several diseases including lung fibrosis and cancer. How exactly MIP-4 is regulated and exerts its role in lung fibrosis remains unclear. Therefore, in the present study, we examined how MIP-4 is regulated and whether it acts via its potential receptor Nir-1.
Materials and methods: A549 cells were grown and maintained in DMEM : F12 (1 : 1) and supplemented with 10% FBS and 1000 U of penicillin/streptomycin and maintained as recommended by the manufacturer (ATCC). Cell migration and invasion, immunohistochemistry (IHC), Western blot, qPCR, and siRNA Nir-1 were used to determine MIP-4 regulation and its role in cell migration.
Results: Cell migration was increased following stimulation of cells with recombinant (r) MIP-4 and bleomycin (BLM), whereas quenching rMIP-4 with its antibody (Ab) or addition of the Ab to BLM or H2O2 diminished rMIP-4-induced cell migration. Along with cell migration, rMIP-4, BLM, and H2O2 induced the formation of actin filaments dynamic structures whereas costimulation with MIP-4 Ab limited BLM- and H2O2-induced effects. MIP-4 mRNA and protein were increased by BLM and H2O2, and the addition of its Ab significantly reduced treatments effect. Experiments with siRNA investigating whether Nir-1 is a potential MIR-4 receptor indicated that the inhibition of Nir-1 decreased cell migration/invasion but did not totally inhibit rMIP-4-induced cell migration.
Conclusion: Therefore, our data indicate that MIP-4 is regulated by BLM and H2O2 and costimulation with its Ab limits the effects on MIP-4 and that the Nir-1 receptor partially mediates MIP-4's effects on increased cell migration. These data also evidenced that MIP-4 is regulated by fibrotic and oxidative stimuli and that quenching MIP-4 with its Ab or therapeutically targeting the Nir-1 receptor may partially limit MIP-4 effects under fibrotic or oxidative stimulation.
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