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

• Published in: BMC immunology 2010-10, Vol.11 (1), p.52-52, Article 52
• Main Authors: Joshi, Amrita D, Oak, Sameer R, Hartigan, Adam J, Finn, William G, Kunkel, Steven L, Duffy, Karen E, Das, Anuk, Hogaboam, Cory M
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Bone marrow; Cells, Cultured; Chemokine CCL3 - biosynthesis; Chemokine CCL3 - genetics; Chemokine CCL3 - immunology; Chemokines; 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; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Humans; Immune response; Immune system; Interleukin-1; 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; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Mannose-Binding Lectins - biosynthesis; Mannose-Binding Lectins - genetics; Medical research; Physiological aspects; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Regulation; Studies; Th1-Th2 Balance
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/1471-2172-11-52

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. 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. 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.