title: Interleukin-6 enhances whereas tumor necrosis factor alpha and interferons inhibit integrin expression and adhesion of human mast cells to extracellular matrix proteins.
abstract: Integrins are expressed on mast cells and constitute an essential prerequisite for the accumulation of the cells at sites of inflammation. In order to clarify a potential contribution of inflammatory cytokines to this process, we have studied the modulation of integrin expression and adhesion of immature human mast cells (HMC-1) to extracellular matrix proteins by interleukin-6, tumor necrosis factor alpha, interferon-alpha and interferon-gamma. Corticosteroids were used for comparison. On fluorescence-activated cell sorter analysis, preincubation of cells for 48 h with different concentrations of interleukin-6 induced a significant, up to 40%, increase of alpha v alpha 5, CD49b (alpha 2), CD49e (alpha 5), CD49f (alpha 6), and CD51 (alpha v). In contrast, different concentrations of tumor necrosis factor alpha, interferon-alpha, interferon-gamma, and dexamethasone (10-8-10-10 M) inhibited expression of adhesion receptors by up to 60%, reaching significance for some but not all integrins. On semiquantitative polymerase chain reaction analysis, interleukin-6, the other cytokines, and corticosteroids significantly modulated expression of alpha1, alpha v and alpha 5 integrin chains at mRNA level. Functional significance of these findings was proven in adhesion assays using fibronectin, laminin, and vitronectin, with interleukin-6 causing significant enhancement of adhesion in all cases, tumor necrosis factor alpha and dexamethasone inducing significant reduction of adhesion to fibronectin and laminin, and interferon-gamma significantly inhibiting adhesion to fibronectin only. Specificity of interleukin-6-induced changes was demonstrated using antibodies against alpha1 and alpha 5 integrins in unstimulated and interleukin-6-prestimulated cells. These data show that interleukin-6 stimulates mast cell adhesion to extracellular matrix and thus allows for the accumulation of the cells at tissue sites by enhancing integrin expression, whereas tumor necrosis factor alpha, interferon-alpha, interferon-gamma, and dexamethasone downmodulate this process.
authors.affiliation: Department of DermatologyCharité, Humboldt University, Berlin, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Schoeler
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
authors.forename: Beate M
authors.initials: BM
authors.lastname: Henz
authors.forename: Jens
authors.initials: J
authors.lastname: Küchler
authors.forename: Sabine
authors.initials: S
authors.lastname: Krüger-Krasagakis
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion; D002469:Cell Separation; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D039421:Integrin alpha2 / Q000096:biosynthesis; D039482:Integrin alpha5 / Q000096:biosynthesis; D039503:Integrin alpha6 / Q000096:biosynthesis; D039564:Integrin alphaV / Q000096:biosynthesis; D016023:Integrins / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D039421:Integrin alpha2; D039482:Integrin alpha5; D039503:Integrin alpha6; D039564:Integrin alphaV; D016023:Integrins; D016898:Interferon-alpha; D015850:Interleukin-6; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D007372:Interferons