The human cathelicidin, LL-37, kills through activation of the mitochondrial-associated pathway of apoptosis in a caspase-independent manner
Bibliographic record
Abstract
A47 LL-37 is a human cationic host defense peptide that belongs to the cathelicidin family of antimicrobial peptides. LL-37 is expressed by a variety of cell types, including neutrophils and epithelial cells, which release the peptide in response to numerous inflammatory stimuli. Upon release, LL-37 acts as an effector molecule of innate immunity, displaying both antimicrobial and immunomodulatory activities. In addition, LL-37 has been shown to have antitumorigenic activity, however, the specific mechanism(s) of LL-37-induced cell death has not been examined. We have found that LL-37 kills Jurkat T leukemia cells via apoptosis, leading to DNA fragmentation and phosphatidylserine externalization. We have verified apoptosis through Hoechst 33342 staining analysis, where we observed chromatin condensation and apoptotic body formation. We also detected a loss of mitochondrial membrane potential. Additionally, LL-37-induced apoptosis is independent of caspase family members, in that a broad spectrum caspase inhibitor (Z-VAD-fmk), as well as a specific caspase-2 inhibitor (Z-VDVAD-fmk), had no effect on LL-37-induced killing. We defined the specific apoptotic pathway induced by LL-37 through the utilization of Jurkat T leukemia cells modified to express antiapoptotic proteins at high levels (ie.Bcl-2), as well as cells that are deficient in various proteins associated with apoptosis (ie.Bax). Of interest, we found that both Bcl-2 overexpressing Jurkat cells, as well as cells which are deficient in Bax and Bak proteins displayed a significant reduction in LL-37-induced apoptosis. In addition, Jurkat cells that have been modified in the Fas-receptor associated pathway, including Fas-associated death domain-containing protein (FADD) knockout and caspase-8 knockout cells, showed no reduction in apoptosis when exposed to LL-37. Together, these data show that LL-37 is leading to apoptosis in Jurkat T leukemia cells via a caspase-independent, mitochondria-associated pathway of apoptosis.
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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) | 0.001 | 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".