Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5'-AMP. Acting through the adenosine A2b receptor (A2bR), the luminally derived adenosine induces vectorial chloride secretion and a polarized secretion of interleukin-6 to the intestinal lumen. Although some G protein-coupled receptors interact with anchoring or signaling molecules, not much is known in this critical area for the A2bR. We used the model intestinal epithelial cell line, T84, and Caco2-BBE cells stably transfected with GFP-A2b receptor to study the intestinal A2bR. The A2bR is present in both the apical and basolateral membranes of intestinal epithelia. Apical or basolateral stimulation of the A2bR induces recruitment of the receptor to the plasma membrane and caveolar fractions. The A2bR co-immunoprecipitates with E3KARP and ezrin upon agonist stimulation. Ezrin interacts with E3KARP and PKA and the interaction between ezrin and E3KARP is enhanced by agonist stimulation. Our data suggest that the A2bR is recruited to the plasma membrane upon apical or basolateral agonist stimulation and interacts with E3KARP and ezrin. We speculate that such an interaction may not only anchor the A2bR to the plasma membrane but may also function to stabilize the receptor in a signaling complex in the plasma membrane.
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PMID:The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation. 1208 47

Pain associated with oral squamous cell carcinoma (oral SCC) decreases quality of life and survival. The interaction between cancer and the peripheral nerves is known to initiate and amplify pain and contribute to carcinogenesis. Schwann cells envelop peripheral nerves and are activated in response to neuronal damage. The contributions of Schwann cells to oral SCC progression and pain are unknown. Using a non-contact co-culture model, we demonstrate that Schwann cells (RSC-96) and oral SCC cells (HSC-3) reciprocally interact to promote proliferation, migration, and invasion. Schwann cell-oral SCC interaction leads to increased production of adenosine, which stimulates cell proliferation and migration of both cell types. The adenosine receptor A2B (ADORA2B) is expressed on RSC-96 cells. We show that supernatant from the RSC-96 cells co-cultured with HSC-3 cells induces increased mechanical hypersensitivity in mice compared to supernatant from control RSC-96 cells. Treatment with the ADORA2B antagonist PSB603 significantly inhibits co-culture interactions - proliferation and migration, and co-culture supernatant induced mechanical hypersensitivity. RSC-96 cells co-cultured with HSC-3 cells secrete increased amounts of the pronociceptive mediator, interleukin-6 (IL-6), which can be reduced by adding PSB603 into the co-culture. Our data support a reciprocal interaction between oral SCC and Schwann cells mediated by adenosine with potential to promote oral SCC progression and pain via increased secretion of IL-6.
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PMID:Reciprocal interactions between cancer and Schwann cells contribute to oral cancer progression and pain. 3081