Protein Phosphatase 2A and Protein Kinase Cα Are Physically Associated and Are Involved in Pseudomonas aeruginosa-induced Interleukin 6 Production by Mast Cells
Bibliographic record
Abstract
Pulmonary infection with Pseudomonas aeruginosa is characterized by massive airway inflammation, which comprises significant cytokine production. Although mast cells are abundant in the lung and are potent sources of various cytokines, a role of mast cells in P. aeruginosa infection remains undefined, and P. aeruginosa-induced signaling mechanisms in mast cells have not been studied previously. Here we demonstrate that human cord blood-derived mast cells, mouse bone marrow-derived mast cells, and the mouse mast cell line MC/9 produce significant amounts of interleukin 6 (IL-6) in response to P. aeruginosa. This response was accompanied by a stimulation of protein kinase Calpha (PKCalpha) phosphorylation and PKC activity and was significantly blocked by the PKC inhibitors Ro 31-8220 and PKCalpha pseudosubstrate. Interestingly, mast cells treated with P. aeruginosa had reduced protein levels of phosphatase 2A catalytic unit (PP2Ac), which prompted us to determine whether a direct association between PKCalpha and PP2A occurs in mast cells. In mouse bone marrow-derived mast cells and MC/9 cells, as well as in the human mast cell line HMC-1, PP2A coimmunoprecipitated with PKCalpha either using PKCalpha- or PP2Ac-specific antibodies, suggesting that PKCalpha and PP2Ac are physically associated in mast cells. The PP2A inhibitor okadaic acid induced P. aeruginosa-like responses in mast cells including increased PKCalpha phosphorylation, stimulated PKC activity, and augmented IL-6 production, the last being blocked by the PKC inhibitor Ro 31-8220. Finally, okadaic acid potentiated the P. aeruginosa-induced IL-6 production. Collectively, these data provide, to our knowledge, the first evidence of both a direct physical association of PP2A and PKCalpha in mammalian cells and their coinvolvement in regulating mast cell activation in response to P. aeruginosa.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".