title: Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of inflammatory activators and hypoxia.
abstract: Caveolins are specific proteins involved in regulation of signal transduction to intracellular space. Still, their contribution to immune functions has not been completely clarified. Thus, we decided to characterize the expression of caveolins in bone marrow-derived macrophages (BMDMs) under resting and inflammatory conditions. The effect of classical activators (lipopolysaccharide, LPS; interferon-gamma, IFN-γ) was further potentiated with hypoxic (5% O2) conditions. The activation of p44/42-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and expression of caveolin-1, -2, and -3, hypoxia inducible factor-1 alpha (HIF-1α), as well as inducible nitric oxide synthase (iNOS) was monitored using the Western blot technique. The production of nitric oxide (NO) and tumor necrosis factor-alpha (TNFα) was analyzed by Griess method or ELISA, respectively. BMDMs were also transfected with siRNA against caveolin-2. Importantly, our study showed for the first time that BMDMs expressed only caveolin-2, and its level decreased after activation of macrophages with LPS, IFN-γ, and/or hypoxia. The expression of caveolin-2 negatively correlates with the iNOS and HIF-1α protein levels, as well as with the LPS/IFN-γ- and hypoxia-induced activation of ERK1/2. We concluded that caveolin-2 is most probably involved in regulation of pro-inflammatory responses of BMDMs, triggered via activation of ERK1/2.
authors.affiliation: Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, 611 37 Brno, Czech Republic; Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Maceckova
authors.affiliation: Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, 611 37 Brno, Czech Republic; Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Martiskova
authors.affiliation: Department of Animal Physiology and Immunology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlarska 267/2, 611 37 Brno, Czech Republic; Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Adolf
authors.initials: A
authors.lastname: Koudelka
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kubala
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic. Electronic address: pekarovam@ibp.cz.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarova
mesh_terms: D000818:Animals; D051243:Caveolin 2 / Q000235:genetics* / Q000378:metabolism*; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051243:Caveolin 2; D016207:Cytokines; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Caveolin-2; Hypoxia; Inflammation; Interferon-gamma; Lipopolysaccharide; Macrophage