SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Yeddula Narayana; Kushagra Bansal; Akhauri Yash Sinha; Nisha Kapoor; Germain Puzo; Martine Gilleron; Kithiganahalli Narayanaswamy Balaji

doi:10.1016/j.molimm.2009.06.019

SOCS3 expression induced by PIM2 requires PKC and PI3K signaling

Mol Immunol. 2009 Sep;46(15):2947-54. doi: 10.1016/j.molimm.2009.06.019. Epub 2009 Jul 15.

Authors

Yeddula Narayana¹, Kushagra Bansal, Akhauri Yash Sinha, Nisha Kapoor, Germain Puzo, Martine Gilleron, Kithiganahalli Narayanaswamy Balaji

Affiliation

¹ Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India.

PMID: 19608279
DOI: 10.1016/j.molimm.2009.06.019

Abstract

Initiation of proinflammatory host immunity in response to infection represents as a key event in effective control and containment of the pathogen at the site of infection as well as in elicitation of robust immune memory responses. In the current investigation, we demonstrate that an integral cell wall antigen of the mycobacterial envelope, Phosphatidyl-myo-inositol dimannosides (PIM2) triggers Suppressor of cytokine signaling (SOCS) 3 expression in macrophages in a Toll-like receptor 2 (TLR2)-MyD88 dependent manner. Data derived from signaling perturbations suggest the involvement of phosphoinositide-3 kinase (PI3K) and protein kinase C (PKC) signaling pathways during PIM2 induced SOCS3 expression. Further, pharmacological inhibition of ERK1/2, but not of p38 MAP kinase or JNK abrogated the induced expression of SOCS3. The PIM2 induced activation of ERK1/2 was dependent on the activation of PI3K or PKC signaling which in turn regulated p65 nuclear factor -kappaB (NF-kappaB) nuclear translocation. Overall, current study delineates the role for PI3K-PKC axis and ERK1/2 signaling as key signaling events during PIM2 induced SOCS3 expression in macrophages.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Down-Regulation / genetics
Down-Regulation / immunology
Gene Knockdown Techniques
Macrophages / drug effects
Macrophages / immunology*
Macrophages / metabolism
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / immunology
Mitogen-Activated Protein Kinases / metabolism*
Myeloid Differentiation Factor 88 / genetics
Myeloid Differentiation Factor 88 / immunology
Myeloid Differentiation Factor 88 / metabolism
NF-kappa B / antagonists & inhibitors
NF-kappa B / immunology
NF-kappa B / metabolism
Phosphatidylinositol 3-Kinases / immunology
Phosphatidylinositol 3-Kinases / metabolism*
Phosphatidylinositols / immunology*
Phosphatidylinositols / pharmacology
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / immunology
Protein Kinase C / metabolism*
Protein Kinase Inhibitors / pharmacology
RNA, Small Interfering / immunology
RNA, Small Interfering / metabolism
Signal Transduction / drug effects
Signal Transduction / immunology
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / agonists
Suppressor of Cytokine Signaling Proteins / immunology
Suppressor of Cytokine Signaling Proteins / metabolism*
Toll-Like Receptor 2 / genetics
Toll-Like Receptor 2 / immunology
Toll-Like Receptor 2 / metabolism

Substances

Myd88 protein, mouse
Myeloid Differentiation Factor 88
NF-kappa B
Phosphatidylinositols
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors
RNA, Small Interfering
Socs3 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Tlr2 protein, mouse
Toll-Like Receptor 2
phosphatidylinositol dimannoside
Protein Kinase C
Mitogen-Activated Protein Kinases