The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-α responses
Open accessAbstract
Lipopolysaccharide (LPS) stimulation of the innate immune response requires the activation of signaling cascades that culminate in the synthesis and secretion of proinflammatory cytokines. Given the inhibitory effects of phosphodiesterase (PDE) inhibitors on LPS-induced cytokine production, we have investigated LPS responses in mice deficient in PDE4 (type 4 cAMP-specific PDE)-B and PDE4D. LPS stimulation of mouse peripheral leukocytes induced PDE4B mRNA accumulation and increased PDE4 activity. This response was completely absent in mice deficient in PDE4B but not PDE4D. LPS induction of tumor necrosis factor-α secretion by circulating leukocytes was decreased by approximately 90% in mice deficient in PDE4B but not in mice lacking PDE4D. The impaired LPS response was evident regardless of the LPS dose used for stimulation and was associated with a more than 90% decrease in tumor necrosis factor-α mRNA accumulation. A decreased responsiveness to LPS was also present in other inflammatory cells, including peritoneal and lung macrophages. These findings demonstrate that PDE4B gene activation by LPS constitutes a feedback regulation essential for an efficient immune response.
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Cited by
Padmos, R. C., Hillegers, M. H. J., Knijff, E. M., Vonk, R., Bouvy, A., Staal, F. J. T., de Ridder, D., Kupka, R. W., Nolen, W. A., & Drexhage, H. A. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.4.395 · Cited by 336
Rabe, K. F. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01218.x · Cited by 273
Robichaud, A., Stamatiou, P. B., Jin, S.-L. C., Lachance, N., MacDonald, D., Laliberté, F., Liu, S., Huang, Z., Conti, M., & Chan, C.-C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15506 · Cited by 267
Self-citationRole of cAMP and phosphodiesterase signaling in liver health and disease
Wahlang, B., McClain, C., Barve, S., & Gobejishvili, L. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.06.005 · Cited by 168
Zhou, M., Xu, R., Kaelber, D. C., & Gurney, M. E. (2020) · PLOS ONE · doi:10.1371/journal.pone.0229819 · Cited by 157
Metadata
- Authors
- Jin, S.-L. C., & Conti, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-05-21
- Volume
- 99
- Issue
- 11
- Pages
- 7628-7633
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2159269771
- Cited by
- 367
- References
- 48
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- green
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