We have recently demonstrated that liposomes composed of phosphatidylserine (PS-liposomes) suppressed nitric oxide and inflammatory cytokine productions following LPS stimulation in macrophages. In this study, we examined the effect of PS-liposomes on expressions of TLR-4 and MyD88, which are essential for the signal transduction in LPS stimulation. Expression of MyD88 was suppressed when macrophages were treated with PS-liposomes, but not with liposomes of phosphatidylcholine. No change in TLR-4 expression was observed. MyD88 suppression was restored to the control levels when cells were pre-treated with anti-TGF- β antibody, suggesting that TGF- β plays an important role in down-regulation of MyD88 following PS-liposome treatment.
R. E. Ellis, J. Y. Yuan and H. R. Horvitz, “Mechanisms and Functions of Cell Death,” Annual Reviews of Cell Biology, Vol. 7, 1991, pp. 663-698.
C. B. Thompson, “Apoptosis in the Pathogenesis and Treatment of Disease,” Science, Vol. 267, No. 5203, 1995, pp. 1456-1462. doi:10.1126/science.7878464
S. S. Bacus, A. V. Gudkov, M. Lowe, L. Lyass, Y. Yung, A. P. Komarov, K. Keyomarsi, Y. Yarden and R. Seger, “Taxol-Induced Apoptosis Depends on MAP Kinase Pathways (ERK and p38) and Is Independent of p53,” Oncogene, Vol. 20, No. 2, 2001, pp. 147-155. doi:10.1038/sj.onc.1204062
Y. Fujiwara, K. Kawada, D. Takano, S. Tanimura, K. Ozaki and M. Kohno, “Inhibition of the PI3 Kinase/Akt Pathway Enhances Doxorubicin-Induced Apoptotic Cell Death in Tumor Cells in a p53-Dependent Manner,” Biochemical Biophysical Research Communications, Vol. 340, No. 2, 2006, pp. 560-566. doi:10.1016/j.bbrc.2005.12.039
P. M. Henson and D. A. Hume, “Apoptotic Cell Removal in Development and Tissue Homeostasis,” Trends Immunology, Vol. 27, No. 5, 2006, pp. 244-250. doi:10.1016/j.it.2006.03.005
V. A. Fadok, D. L. Bratton and P. M. Henson, “Phagocyte Receptors for Apoptotic Cells: Recognition, Uptake, and Consequences,” Journal of Clinical Investigation, Vol. 108, No. 7, 2001, pp. 57-962.
C. N. Serhan and J. Savill, “Resolution of Inflammation: The Beginning Programs the End,” Nature Immunology, Vol. 6, No. 12, 2005, pp. 1191-1197. doi:10.1038/ni1276
V. A. Fadok, D. L. Bratton, S. C. Frasch, M. L. Warner and P. M. Henson, “The Role of Phosphatidylserine in Recognition of Apoptotic Cells by Phagocytes,” Cell Deathand Differentiation, Vol. 5, No. 7, 1998, pp. 551562. doi:10.1038/sj.cdd.4400404
J. Savilland C. Gregory, “Apoptotic PS to Phagocyte TIM-4: Eat Me,” Immunity, Vol. 27, No. 6, 2007, pp. 830-832. doi:10.1016/j.immuni.2007.12.002
V. A. Fadok, D. L. Bratton, A. Konowal P. W. Freed, J. Y. Westcott and P. M. Henson, “Macrophages that Have Ingested Apoptotic Cells in Vitro Inhibit Proinflammatory Cytokine Production through Autocrine/Paracrine Mechanisms Involving TGF-β, PGE2, and PAF,” Journal of Clinical Investigation, Vol. 101, No. 4, 1998, pp. 890898. doi:10.1172/JCI1112
V. A. Fadok, D. L. Bratton, D. M. Rose, A. Pearson, R. A. Ezekewitz and P. M. Henson, “Phosphatidylserine-Specific Clearance of Apoptotic Cells,” Nature, Vol. 405, No. 6782, 2000, pp. 85-90. doi:10.1038/35011084
S. H. Schilling, “A Multipotential Cytokine,” In: B. Hjelmel, J. N. Rich and X. F. Wang, Eds., TGF-Family, Cold Spring Harbor, The TGF-Laboratory Press, New York, 2008, pp. 45-78.
R. W. Vandivier, V. A. Fadok, P. R. Hoffmann, D. L. Bratton, C. Penvari, K. K. Brown, J. D. Brain, F. J. Accurso and P. M. Henson, “Elastase-Mediated Phosphatidylserine Receptor Cleavage Impairs Apoptotic Cell Clearance in Cystic Fibrosis and Bronchiectasis,” Journal of Clinical Investigation, Vol. 109, No. 5, 2002, pp. 661670.
R. Matsuno, Y. Aramak and S. Tsuchiya, “Involvement of TGF-β in Inhibitory Effects of Negatively Charged Liposomes on Nitric Oxide Production by Macrophages Stimulated with LPS,” Biochemical Biophysical Research Communications, Vol. 281, No. 3, 2001, pp. 614-620. doi:10.1006/bbrc.2001.4419
P. R. Hoffmann, J. A. Kench, A. Vondracek, E. Kruk, D. L. Daleke, M. Jordan, P. Marrack P. M. Henson and V. A. Fadok, “Interaction between Phosphatidylserine and the Phosphatidylserine Receptor Inhibits Immune Responses in Vivo,” Journal of Immunology, Vol. 174, No. 3, 2005, pp. 1393-1404.
Y. Aramaki, F. Nitta, R. Matsuno, Y. Morimura and S. Tsuchiya, “Inhibitory Effects of Negatively Charged Liposomes on Nitric Oxide Production from Macrophages Stimulated by LPS,” Biochemical Biophysical Research Communications, Vol. 220, No. 1, 1996, pp. 1-6. doi:10.1006/bbrc.1996.0346
M. Otsuka, K. Goto, S. Tsuchiya and Y. Aramaki, “Phosphatidylserine-Specific Receptor Contributes to TGF-β Production in Macrophages through a MAP Kinase, ERK,” Biological Pharmaceutical Bulletin, Vol. 28, No. 9, 2005, pp. 1707-1710. doi:10.1248/bpb.28.1707
M. Otsuka, Y. Negishi and Y. Aramaki, “Involvement of Phosphatidylinositol-3-Kinase and ERK Pathways in the Production of TGF-β1 by Macrophages Treated with Liposomes Composed of Phosphatidylserine,” FEBS Letters, Vol.581, No. 3, pp. 25-330.
P. J. Godowski, “A Smooth Operator for LPS Responses,” Nature Immunology, Vol. 6, No. 6, 2005, pp. 544-546. doi:10.1038/ni0605-544
S. Akira and K. Takeda “Toll-Like Receptor Signaling,” Nature Review Immunology, Vol. 4, No. 7, 2004, pp. 499-511. doi:10.1038/nri1391
T. Kawai, O. Adachi, T. Ogawa, K. Takeda and S. Akira, “Unresponsiveness of MyD88-Deficient Mice to Endotoxin,” Immunity, Vol. 11, No. 1, 1999, pp. 115-122. doi:10.1016/S1074-7613(00)80086-2
Y. Aramaki, R. Matsuno and S. Tsuchiya, “Involvement of p38 MAP Kinase in the Inhibitory Effects of Phosphatidylserine Liposomes on Nitric Oxide Production from Macrophages Stimulated with LPS,” Biochemical Biophysical Research Communications, Vol. 280, No. 4, 2001, pp. 982-987. doi:10.1006/bbrc.2000.4204
K. Takeda, T. Kaisho and S. Akira, “Toll-Like Receptors,” Annual Review Immunology, Vol. 21, 2003, pp. 335-376. doi:10.1146/annurev.immunol.21.120601.141126
S. Das, K. Pandey, A. Kumar, A. H. Sardar, B. Purkait, M. Kumar, S. Kumar, V. N. Ravidas, S. Roy, D. Singh and P. Das, “TGF-β1 Re-Programs TLR4 Signaling in L. donovani Infection: Enhancement of SHP-1 and UbiquitinEditing Enzyme A20,” Immunological Cell Biology, Vol. 90, No. 6, 2011, pp. 640-654. doi:10.1038/icb.2011.80
K. L. Jones, A. Mansell, S. Patella, B. J. Scott, P. Hedger, D. M. Kretse and D. J. Phillips, “Activin A Is a Critical Component of the Inflammatory Response, and Its Binding Protein, Follistatin, Reduces Mortality in Endotoxemia,” Proceedings of the National Academy of Sciences in USA, Vol. 104, No. 41, 2007, pp. 16239-16244.
R. Matsuno, Y. Aramaki, H. Arima, Y. Adachi, N. Ohno, T. Yadomae and S. Tsuchiya, “Contribution of CR3 to Nitric Oxide Production from Macrophages Stimulated with High-Dose of LPS,” Biochemical Biophysical Research Communications, Vol. 244, No. 1, 1998, pp. 115119. doi:10.1006/bbrc.1998.8231
C. G. Freire-de-Lima, Y. Q. Xiao, S. J. Gardai, D. L. Bratton, W. P. Schiemann and P. M. Henson, “Apoptotic Cells, through Transforming Growth Factor-Beta, Coordinately Induce Anti-Inflammatory and Suppress Pro-Inflammatory Eicosanoid and No Synthesis in Murine Macrophages,” Journal of Biological Chemistry, Vol. 281, No. 50, 2006, pp. 38376-38384. doi:10.1074/jbc.M605146200
S. Nagata, “Apoptosis and Autoimmune Diseases,” Annals New York Academy of Sciences, Vol. 1209, pp. 10-16. doi:10.1111/j.1749-6632.2010.05749.x
F. Bonnefoy, S. Perruche,M. Couturier, A. Sedrati, Y. Sun, P. Tiberghien, B. Gaugler and P. Saas, “Plasmacytoid Dendritic Cells Play a Major Role in Apoptotic Leukocyte-Induced Immune Modulation,” Journal of Immunology, Vol. 186, No. 10, 2011, pp. 5696-5705. doi:10.4049/jimmunol.1001523
K. Köröskényi, E. Duró, A. Pallai, Z. Sarang, D. Kloor, D. S. Ucker, S. Beceiro, A. Castrillo, A. Chawla, C. A. Ledent, L. Fésüs and Z. Szondy, “Involvement of Adenosine A2A Receptors in Engulfment-Dependent Apoptotic Cell Suppression Ofinflammation,” Journal of Immunology, Vol. 186, No. 122, 2011, pp. 7144-7155.
L. M. Stuart and R. A. B. Ezekowitz, “Phagocytosis: Elegant Complexity,” Immunity, Vol. 22, No. 5, 2005, pp. 539-550. doi:10.1016/j.immuni.2005.05.002
Y. Naiki, K. S.Michelsen, W. Zhang, S. Chen, T. M. Doherty and M. Arditi, “Transforming Growth Factor-Beta Differentially Inhibits MyD88-Dependent, but Not TRAMand TRIF-Dependent, Lipopolysaccharide-Induced TLR4 Signaling,” Journal of Biological Chemistry, Vol. 280, No. 7, 2004, pp. 5491-5495. doi:10.1074/jbc.C400503200