Interleukin-6 enhances whereas tumor necrosis factor alpha and interferons inhibit integrin expression and adhesion of human mast cells to extracellular matrix proteins

J Invest Dermatol. 2003 May;120(5):795-801. doi: 10.1046/j.1523-1747.2003.12126.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Cell Adhesion
  • Cell Separation
  • Dexamethasone / pharmacology
  • Down-Regulation
  • Extracellular Matrix / metabolism*
  • Flow Cytometry
  • Humans
  • Integrin alpha2 / biosynthesis
  • Integrin alpha5 / biosynthesis
  • Integrin alpha6 / biosynthesis
  • Integrin alphaV / biosynthesis
  • Integrins / metabolism*
  • Interferon-alpha / metabolism
  • Interferon-gamma / pharmacology
  • Interferons / metabolism*
  • Interleukin-6 / metabolism*
  • Mast Cells / cytology*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Integrin alpha2
  • Integrin alpha5
  • Integrin alpha6
  • Integrin alphaV
  • Integrins
  • Interferon-alpha
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Interferon-gamma
  • Interferons