In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 152.23-152.23
Abstract:
Pde3B hydrolyzes both cAMP and cGMP, important second messengers in a variety of cellular processes. Pde3B has been shown to regulate NLRP3 inflammasome activity in adipose tissue. To understand whether Pde3B plays a role in the macrophage response to bacterial infection, we derived macrophages from the bone marrow of wildtype and Pde3B knockout mice. Macrophages were then stimulated with LPS for 6 h or left untreated, and total RNA was prepared for RNA-seq analyses. Our data indicate that Pde3B expression was inhibited by LPS in macrophages. Knockout of Pde3B resulted in significant changes in the expression of a large group of genes: 427 genes were up-regulated by at least 2-fold while 428 genes were down-regulated by more than 50% in LPS stimulated macrophages as the result of Pde3B deficiency. Gene profiling indicates that a number of biological processes are affected by Pde3B knockout, including cellular ion/cation homeostasis, immune system processes, and chemotaxis. Interestingly, Pde3B deficiency disturbed the expression of several chemokines: Cxcl-1, -2, and -3 expression were decreased by 96, 60, and 75%, respectively. In contrast, Ccl-4, -7, -12, -22, Cxcl-9 and -l11 expression were enhanced 1.8, 1.5, 1.9, 2, 3, and 3-fold, respectively. Differential expression of dual specificity phosphatase (Dusp)-1, -2, -3, -4, -5, -6, -10, -11, and -16 were also seen between LPS-stimulated wildtype and Pde3B-deficient macrophages. Since the Dusps are important regulators of MAP kinases that control the expression of chemokines, alterations in the expression of Dusps provides a plausible explanation for the changes in chemokine expression. Our studies suggest that Pde3B may regulate chemokine expression via modulating MAP kinases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.152.23
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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