Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages

BMC Immunol. 2010 Oct 19;11:52. doi: 10.1186/1471-2172-11-52.


Background: Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined.

Results: Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone.

Conclusions: Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cells, Cultured
  • Chemokine CCL3 / biosynthesis*
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / immunology
  • Chemokines, CC / biosynthesis*
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Complement Pathway, Alternative / drug effects
  • Complement Pathway, Classical / drug effects
  • Cytokines / immunology
  • Cytokines / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / genetics
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mannose-Binding Lectins / biosynthesis
  • Mannose-Binding Lectins / genetics
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Th1-Th2 Balance


  • Biomarkers
  • CCL18 protein, human
  • Chemokine CCL3
  • Chemokines, CC
  • Cytokines
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Lectins, C-Type
  • Lipopolysaccharides
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor