Publications by authors named "E Wahle"
Study Question: Does the chemokine/chemokine receptor axis, involved in immune cell trafficking, contribute to the pathology of testicular inflammation and how does activin A modulate this network?
Summary Answer: Testicular chemokines and their receptors (especially those essential for trafficking of monocytes) are elevated in orchitis, and activin A modulates the expression of the chemokine/chemokine receptor network to promote monocyte/macrophage and T cell infiltration into the testes, causing extensive tissue damage.
What Is Known Already: The levels of CC motif chemokine receptor (CCR)2 and its ligand CC motif chemokine ligand (CCL)2 are increased in experimental autoimmune orchitis (EAO) compared with healthy testes, and mice deficient in CCR2 are protected from EAO-induced tissue damage. Activin A induces CCR2 expression in macrophages, promoting their migration.
In Vitro Reconstitution of the Drosophila melanogaster CCR4-NOT Complex to Assay Deadenylation.
Methods Mol Biol
October 2023
The CCR4-NOT complex is a multi-subunit poly(A)-specific 3' exoribonuclease that catalyzes the deadenylation of mRNA. In this chapter, we describe procedures to express and purify recombinant Drosophila melanogaster CCR4-NOT. Furthermore, we provide protocols for preparing radioactively labeled RNA substrates and conducting in vitro deadenylation assays.
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- Posttranscriptional regulation of nanos mRNA is crucial for the development of the anterior-posterior axis in Drosophila embryos, primarily influenced by the protein Smaug binding to specific elements in the mRNA.
- Smaug forms a larger repressor complex that includes several proteins and inhibits nanos translation while promoting its deadenylation via the CCR4-NOT deadenylase complex.
- In vitro experiments show that Smaug can induce deadenylation by recruiting CCR4-NOT components, and while certain subunits like NOT10 and NOT11 are not needed, others are essential for this process, with findings indicating that Smaug enhances the efficiency of deadenylation.
Experimental autoimmune-orchitis (EAO), a rodent model of chronic testicular inflammation and fibrosis, replicates pathogenic changes seen in some cases of human spermatogenic disturbances. During EAO, increased levels of pro-inflammatory and pro-fibrotic mediators such as TNF, CCL2, and activin A are accompanied by infiltration of leukocytes into the testicular parenchyma. Activin A levels correlate with EAO severity, while elevated CCL2 acting through its receptor CCR2 mediates leukocyte trafficking and recruits macrophages.
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