Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages.
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.
Joshi
Amrita D
AD
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Oak
Sameer R
SR
Hartigan
Adam J
AJ
Finn
William G
WG
Kunkel
Steven L
SL
Duffy
Karen E
KE
Das
Anuk
A
Hogaboam
Cory M
CM
D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058408:Th1-Th2 Balance
D015415:Biomarkers; C111792:CCL18 protein, human; D054405:Chemokine CCL3; D019742:Chemokines, CC; D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface