Interleukin-32 induces the differentiation of monocytes into macrophage-like cells

Mihai G. Netea, Eli C. Lewis, Tania Azam, Leo A.B. Joosten, Jun Jaekal, Su Young Bae, Charles A. Dinarello, Soo Hyun Kim

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

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-κB. 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 TNFα, IL-1β, 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.

Original languageEnglish
Pages (from-to)3515-3520
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number9
DOIs
StatePublished - 4 Mar 2008
Externally publishedYes

Keywords

  • Antigen presentation
  • Cytokine
  • Immune cell differentiation
  • Inflammation
  • Muramyl dipeptide

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