IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways

Jae Kwang Yoo, Hyokjoon Kwon, Lee Young Khil, Li Zhang, Hee Sook Jun, Ji Won Yoon

Research output: Contribution to journalArticle

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Abstract

Macrophages are activated during an inflammatory response and produce multiple inflammatory cytokines. IL-18 is one of the most important innate cytokines produced from macrophages in the early stages of the inflammatory immune response. Monocyte chemoattractant protein (MCP-1) is expressed in many inflammatory diseases such as multiple sclerosis and rheumatoid arthritis, and its expression is correlated with the severity of the disease. Both IL-18 and MCP-1 have been shown to be involved in inflammatory immune responses. However, it has been unclear whether IL-18 is involved in the induction of MCP-1. This investigation was initiated to determine whether IL-18 can induce MCP-1 production, and if so, by which signal transduction pathways. We found that IL-18 induced the production of MCP-1 in macrophages, which was IL-12-independent and was not mediated by autocrine cytokines such as IFN-γ or TNF-α. We then examined signal transduction pathways involved in IL-18-induced MCP-1 production. We found that IL-18 did not activate the IκB kinase/NF-κB pathway, evidenced by no degradation of IκBα and no translocation of NF-κB p65 to the nucleus in IL-18-stimulated macrophages. Instead, IL-18 activated the PI3K/Akt and MEK/ERK1/2 pathways. Inhibition of either of these pathways attenuated MCP-1 production in macrophages, and inhibition of both signaling pathways resulted in the complete inhibition of MCP-1 production. On the basis of these observations, we conclude that IL-18 induces MCP-1 production through the PI3K/Akt and MEK/ERK1/2 pathways in macrophages.

Original languageEnglish (US)
Pages (from-to)8280-8286
Number of pages7
JournalJournal of Immunology
Volume175
Issue number12
StatePublished - Dec 15 2005
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Interleukin-18
MAP Kinase Signaling System
Chemokine CCL2
Mitogen-Activated Protein Kinase Kinases
Macrophages
Cytokines
Phosphatidylinositol 3-Kinases
Signal Transduction
Interleukin-12
Multiple Sclerosis
Rheumatoid Arthritis
Phosphotransferases

ASJC Scopus subject areas

  • Immunology

Cite this

IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. / Yoo, Jae Kwang; Kwon, Hyokjoon; Khil, Lee Young; Zhang, Li; Jun, Hee Sook; Yoon, Ji Won.

In: Journal of Immunology, Vol. 175, No. 12, 15.12.2005, p. 8280-8286.

Research output: Contribution to journalArticle

Yoo, Jae Kwang ; Kwon, Hyokjoon ; Khil, Lee Young ; Zhang, Li ; Jun, Hee Sook ; Yoon, Ji Won. / IL-18 induces monocyte chemotactic protein-1 production in macrophages through the phosphatidylinositol 3-kinase/Akt and MEK/ERK1/2 pathways. In: Journal of Immunology. 2005 ; Vol. 175, No. 12. pp. 8280-8286.
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