Abstract
Heat shock response is a self-defense mechanism for protection of cells and organisms from a wide range of harmful Stressors. Recent studies revealed that it is involved in the regulation of cytokines expression. IL-18 is an important cytokine in mediating immune response. We studied LPS-induced IL-18 expression in heat shock treated RAW264.7 murine macrophages. Our results show that the heat shock response significantly inhibited the expression of LPS-induced pro-inflammatory cytokine IL-18. Further research on the down-regulation mechanism shows that this inhibitory effect is correlated to the great suppression of the binding activity of AP-1, which is a transcription factor binding to the promoter of IL-18 (−1120 to −1083) and regulates the transcription of IL-18. Meanwhile, we observed that the phosphorylation of JNK, which is AP-1 upstream kinase, was greatly decreased. These results confirmed that the down-regulation effect on IL-18 production in heat shock response is related to the suppression of the JNK/AP-1 signaling pathway.
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References
Lindquist, S., The heat-shock response, Annu. Rev. Biochem., 1986, 55: 1151–1191.
Morimoto, R. I., Cells in stress: transcriptional activation of heat shock genes, Science, 1993, 259: 1409–1410.
Abbas, A. K., Lichtman, A. H., Pober, J. S., Cellular and Molecular Immunology, 4th ed., Philadelphia, London, New York, St. Louvis, Sydney, Toronto: W. B. Saunders Company, 2000, 236–269.
Snyder, Y. M., Guthrie, L., Evans, G. F. et al., Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages, J. Leukocyte. Biol., 1992, 51: 181–187.
Li, C. L., Wang, X. Y., Zhang, J. S. et al., Heat shock inhibits IL-12 p40 expression through NF-kB signaling pathway in macro-phages, Cytokine, 2001, 16: 153–159.
Wang, X. Y., Zou, Y. Y., Wang, Y. et al., Differential regulation of interleukin-12 and interleukin-10 by heat shock response in murine peritoneal macrophages, Biochem. Biophys. Res. Commun., 2001, 287: 1041–1044.
Nakanishi, K., Yoshimoto, T., Txutsui, H. et al., Interleukin-18 regulates both Thl and Th2 responses, Annu. Rev. Immunol., 2001, 19: 423–474.
Gracie, J. A., Forsey, R. J., Chan, W. L. et al., A. proinflammatory role for IL-18 in rheumatoid arthritis, J. Clin. Invest., 1999, 104: 1393–1401.
Kim, Y. M., Im, J. Y., Han, S. H. et al., IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages, J. Immunol., 2000, 165: 3198–3205.
Davis, R. J., Signal transduction by the JNK group of MAP kinases, Cell, 2000, 103: 239–252.
Bassam, B. J., Anollesm, G. C., Gresshoff, P. M., Fast and sensitive silver staining of DNA in polyacrylamide gels, Anal. Biochem., 1991, 196: 80–83.
Zhang, J. S., Feng, W. G., Li, C. L. et al., NF-kB regulates the LPS-induced expression of interleukin 12 p40 in murine peritoneal macrophages: Roles of PKC, PKA, ERK, p38MAPK, and proteasome, Cellular. Immu., 2000, 204: 38–45.
Jolly, C., Morimoto, R. I., Role of the heat shock response and molecular chaperones in oncogenesis and cell death, J. Natl. Cacer. Inst, 2000, 92: 1564–1572.
Wong, H. R., Finder, J. D., Wasserloos, K. et al., Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is inhibited by the heat shock response, Am. J. Physiol., 1995, 269: L843-L845.
Okamura, H., Nagata, K., Komatsu, T. et al., A. novel costimulatory factor for gamma interferon induction found in the liver of mice causes endotoxic shock, Infect. Immun., 1995, 63: 3966–3972.
Wild, J. S., Sigounas, A., Sur, N. et al., IFN-y-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma, J. Immunol., 2000, 164: 2701–2710.
Gabai, V. L., Meriin, A. B., Mosser, D. D. et al., Hsp70 prevents activation of stress kinase, J. Biol. Chem., 1997, 272: 18033–18037.
Ghosh, S., May, M. J., Kopp, E. B., NF-kB and Rel proteins: evolutionarily conserved mediators of immune responses, Annu. Rev. Immunol., 1998, 16: 225–260.
Zhang, J. S., Wang, Y. X., Shan, Y. A., et al., The research on the transcription factor NF-kB (A review in Chinese), Chinese Science Bulletin, 2002, 47(5): 323–329.
Yoo, C. G., Lee, S., Lee, C. T. et al., Anti-inflammatory effect of heat shock protein induction is related to stabilization of I kappa B alpha through preventing I kappa B kinase activation in respiratory epithelial cells, J. Immunol., 2000, 164: 5416–5423.
Suk, K., Kim, S.Y., Kim, H., Regulation of IL-18 production by IFNy and PGE2 in mouse microglial cells: involvement of NF-kB pathway in the regulatory processes, Immuno. Lett., 2001, 77: 79–85.
Grover, A., Molecular biology of stress responses, Cell Stress & Chaperones, 2002, 7: 1–5.
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Wang, Y., Li, C., Wang, X. et al. Heat shock response downregulates IL-18 expression in the murine macrophage cell line, RAW264.7. Chin.Sci.Bull. 48, 780–785 (2003). https://doi.org/10.1007/BF03187052
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DOI: https://doi.org/10.1007/BF03187052