Interleukin-32 induces the differentiation of monocytes into macrophage-like cells.
After emigration from the bone marrow to the peripheral blood, monocytes enter tissues and differentiate into macrophages, the prototype scavenger of the immune system. By ingesting and killing microorganisms and removing cellular debris, macrophages also process antigens as a first step in mounting a specific immune response. IL-32 is a cytokine inducing proinflammatory cytokines and chemokines via p38-MAPK and NF-kappaB. In the present study, we demonstrate that IL-32 induces differentiation of human blood monocytes as well as THP-1 leukemic cells into macrophage-like cells with functional phagocytic activity for live bacteria. Muramyl dipepide (MDP), the ligand for the intracellular nuclear oligomerization domain (NOD) 2 receptor, has no effect on differentiation alone but augments the monocyte-to-macrophage differentiation by IL-32. Unexpectedly, IL-32 reversed GM-CSF/IL-4-induced dendritic cell differentiation to macrophage-like cells. Whereas the induction of TNFalpha, IL-1beta, and IL-6 by IL-32 is mediated by p38-MAPK, IL-32-induced monocyte-to-macrophage differentiation is mediated through nonapoptotic, caspase-3-dependent mechanisms. Thus, IL-32 not only contributes to host responses through the induction of proinflammatory cytokines but also directly affects specific immunity by differentiating monocytes into macrophage-like cells.
Netea
Mihai G
MG
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Lewis
Eli C
EC
Azam
Tania
T
Joosten
Leo A B
LA
Jaekal
Jun
J
Bae
Su-Young
SY
Dinarello
Charles A
CA
Kim
Soo-Hyun
SH
D001419:Bacteria / Q000276:immunology; D053148:Caspase 3 / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology; D006801:Humans; D007109:Immunity; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D009000:Monocytes / Q000166:cytology*; D010587:Phagocytosis / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016207:Cytokines; C496971:IL32 protein, human; D007378:Interleukins; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3