Interleukin-6 enhances whereas tumor necrosis factor alpha and interferons inhibit integrin expression and adhesion of human mast cells to extracellular matrix proteins.
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.
Schoeler
Dagmar
D
Department of DermatologyCharité, Humboldt University, Berlin, Germany.
Grützkau
Andreas
A
Henz
Beate M
BM
Küchler
Jens
J
Krüger-Krasagakis
Sabine
S
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*
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