The novel H<sub>2</sub>S donor 4‐carboxy‐phenyl isothiocyanate inhibits mast cell degranulation and renin release by decreasing intracellular calcium
Bibliographic record
Abstract
Abstract Background and Purpose Hydrogen sulfide (H2S) modulates many pathophysiological processes, including inflammation and allergic reactions, in which mast cells act as major effector cells. IgE receptor (FcεRI) cross linking leads to an increase in intracellular calcium ([Ca+2]i), a critical step in mast cell degranulation. The aim of this study was to investigate the role of H2S in [Ca+2]i‐dependent mast cell activation. Experimental Approach We investigated the effects of H2S, either endogenously produced or released by the slow H2S donor 4‐carboxy‐phenyl isothiocyanate (PhNCS‐COOH), on antigenic‐ and non‐antigenic degranulation of native murine mast cells, and human and rat (RBL‐2H3) mast cell lines. We measured the release of specific mast cell degranulation markers (β‐hexosaminidase and renin), as well as changes in [Ca+2]i and phosphorylation of proteins downstream of FcεRI activation. Key Results Endogenously produced H2S inhibited antigen‐induced degranulation in RBL‐2H3. Similarly, H2S released by PhNCS‐COOH (10–300 μM) reduced, in a concentration‐dependent manner, antigenic and non‐antigenic degranulation and renin release in all mast cell types. Notably, PhNCS‐COOH also prevented in a concentration‐dependent mode the increase in [Ca+2]i elicited by Ca+2 ionophore, thapsigargin and FcεRI activation. Moreover, PhNCS‐COOH attenuated the phosphorylation of Syk, cPLA‐2 and PLCγ1 in antigen‐stimulated RBL‐2H3 cells. Conclusion and Implications Collectively, our results demonstrate that, by attenuating the phosphorylation of proteins downstream of FcεRI cross‐linking on mast cells, H2S diminishes [Ca+2]i availability and thus mast cell degranulation and renin release. These findings suggest that PhNCS‐COOH could be a strategic therapeutic tool in mast cell‐mediated allergic conditions.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".