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Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation

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Abstract

We have previously reported that a serine/threonine protein kinase, Cot/Tpl2, is a negative regulator of Th1-type immunity through inhibiting IL-12 expression in antigen presenting cells (APCs) stimulated by Toll-like receptor (TLR) ligands. We here show that Cot/Tpl2-/- macrophages produce significantly less IL-23, an important regulator of Th17-type response, than the wild-type counterparts in response to lipopolysaccharide (LPS), which is a ligand for TLR4. The decreased IL-23 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, as the LPS-mediated IL-23 p19 mRNA induction was significantly less in Cot/Tpl2-/- macrophages. Chemical inhibition of extracellular signal-regulated kinase (ERK) activity similarly inhibited IL-23 expression in LPS-stimulated wild-type macrophages. As Cot/Tpl2 is an essential upstream component of the ERK activation pathway of LPS, it is suggested that Cot/Tpl2 positively regulates IL-23 expression through ERK activation. These results indicate that Cot/Tpl2 may be involved in balancing Th1/Th17 differentiation by regulating the expression ratio of IL-12 and IL-23 in APCs.

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Acknowledgements

This work was supported in part by grants from Ministry of Education, Science, and Culture of the Japanese Government.

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Authors and Affiliations

  1. Department of Oral Biochemistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan

    K. Kakimoto, T. Musikacharoen, N. Chiba, K. Bandow, T. Ohnishi & T. Matsuguchi

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  1. K. Kakimoto
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  2. T. Musikacharoen
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  3. N. Chiba
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  4. K. Bandow
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  5. T. Ohnishi
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  6. T. Matsuguchi
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Correspondence to T. Matsuguchi.

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Kakimoto, K., Musikacharoen, T., Chiba, N. et al. Cot/Tpl2 regulates IL-23 p19 expression in LPS-stimulated macrophages through ERK activation. J Physiol Biochem 66, 47–53 (2010). https://doi.org/10.1007/s13105-010-0007-9

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  • DOI: https://doi.org/10.1007/s13105-010-0007-9

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